ORCID Profile
0000-0001-7253-2629
Current Organisation
University of South Australia
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Research Topics
In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Top 5 Research Topics
ANZSRC Field of Research (FoR)
Medical Biotechnology | Veterinary Microbiology (excl. Virology) | Veterinary Parasitology | Characterisation of Biological Macromolecules | Medicinal and Biomolecular Chemistry | Veterinary Epidemiology | Biologically Active Molecules | Veterinary Pharmacology | Veterinary Sciences not elsewhere classified | Veterinary Sciences | Pharmaceutical Sciences | Medical Biotechnology not elsewhere classified |
ANZSRC Socio-Economic Objective (SEO)
Veterinary Pharmaceutical Treatments (e.g. Antibiotics) | Human Pharmaceutical Treatments (e.g. Antibiotics) | Expanding Knowledge in the Chemical Sciences | Expanding Knowledge in the Agricultural and Veterinary Sciences | Livestock Product Traceability and Quality Assurance | Food Safety
Related Links
Publications
Combination Therapy and Nanoparticulate Systems: Smart Approaches for the Effective Treatment of Breast Cancer
Publisher: MDPI AG
Date: 08-06-2020
DOI: 10.3390/PHARMACEUTICS12060524
Abstract: Breast cancer has become one of the biggest concerns for oncologists in the past few decades because of its unpredictable etiopathology and nonavailability of personalized translational medicine. The number of women getting affected by breast cancer has increased dramatically, owing to lifestyle and environmental changes. Besides, the development of multidrug resistance has become a challenge in the therapeutic management of breast cancer. Studies reveal that the use of monotherapy is not effective in the management of breast cancer due to high toxicity and the development of resistance. Combination therapies, such as radiation therapy with adjuvant therapy, endocrine therapy with chemotherapy, and targeted therapy with immunotherapy, are found to be effective. Thus, multimodal and combination treatments, along with nanomedicine, have emerged as a promising strategy with minimum side effects and drug resistance. In this review, we emphasize the multimodal approaches and recent advancements in breast cancer treatment modalities, giving importance to the current data on clinical trials. The novel treatment approach by targeted therapy, according to type, such as luminal, HER2 positive, and triple-negative breast cancer, are discussed. Further, passive and active targeting technologies, including nanoparticles, bioconjugate systems, stimuli-responsive, and nucleic acid delivery systems, including siRNA and aptamer, are explained. The recent research exploring the role of nanomedicine in combination therapy and the possible use of artificial intelligence in breast cancer therapy is also discussed herein. The complexity and dynamism of disease changes require the constant upgrading of knowledge, and innovation is essential for future drug development for treating breast cancer.
Development of an improved Streptococcus uberis experimental mastitis challenge model using different doses and strains in lactating dairy cows
Publisher: Cambridge University Press (CUP)
Date: 20-07-2015
DOI: 10.1017/S0022029915000321
Abstract: Developing a reliable mastitis challenge infection model is required to test new intramammary antimicrobial preparations, other novel bovine mastitis treatments, and study mastitis pathogenesis. Three treatment groups of Holstein Friesian cows in active lactation were administered two doses (10 4 and 10 6 cfu/quarter) on a single occasion with one of the three Streptococcus uberis strains (BFR6019, MFF1283 and SA002) suspended in 5 ml of sterile PBS, administered via intramammary inoculation immediately after milking. All quarters that were challenged with S. uberis strains MLF1283 and BFR6019 showed clinical signs of mastitis on day 1 and 2 after the challenge. Strain SA002 had a lower rate of inducing clinical mastitis which was detected later than day 3 after the challenge. We successfully developed a rapid and reliable model for inducing experimental S. uberis mastitis with 100% success rate in cows in active lactation. On the basis of the correlation results between strains, RAPD fingerprinting results, clinical findings, and a 100% success rate of mastitis induction for low and high doses S. uberis strains MLF1283 and BFR6019, strain virulence seems to be a more important effect than challenge dose in induction of clinical mastitis following experimental challenge.
Advances in Drug-delivery Systems Based on Intrinsically Conducting Polymers
Publisher: The Royal Society of Chemistry
Date: 17-04-2013
DOI: 10.1039/9781849736800-00283
Abstract: Intrinsically conducting polymers (ICPs) are organic polymers with unique capabilities including the ability to conduct electricity. The release of drugs from ICP-based drug delivery systems can be controlled using electrical signaling to alter the redox state of the ICP, leading to subsequent changes in polymer charge and volume. The increasing use of ICPs in drug delivery systems can be attributed to their biocompatible nature and the ability to regulate drug release electrically. Drug can be easily incorporated into these polymers by physical and chemical means. As the release of the drugs from ICPs is in accordance with electrical stimulus the therapeutic effect can be maximized with a reduction in the side effects. In this chapter a general overview of ICPs, their electrochemical properties and the techniques used to characterize these materials with specifics pertaining to drug delivery is provided. Emphasis is given to advances in methods and technology to enhance the drug-loading capacity of these polymers and to achieve precise controlled therapy. The chapter discusses some of the exciting applications of ICPs as devices for controlled delivery of drugs to desired locations.
Stability Studies of Extemporaneously Compounded Clobazam Oral Suspension
Publisher: SAGE Publications
Date: 23-11-2016
Evaluation of Benzguinols as Next-Generation Antibiotics for the Treatment of Multidrug-Resistant Bacterial Infections
Publisher: MDPI AG
Date: 16-06-2021
DOI: 10.3390/ANTIBIOTICS10060727
Abstract: Our recent focus on the “lost antibiotic” unguinol and related nidulin-family fungal natural products identified two semisynthetic derivatives, benzguinols A and B, with unexpected in vitro activity against Staphylococcus aureus isolates either susceptible or resistant to methicillin. Here, we show further activity of the benzguinols against methicillin-resistant isolates of the animal pathogen Staphylococcus pseudintermedius, with minimum inhibitory concentration (MIC) ranging 0.5–1 μg/mL. When combined with sub-inhibitory concentrations of colistin, the benzguinols demonstrated synergy against Gram-negative reference strains of Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa (MICs of 1–2 μg/mL in the presence of colistin), whereas the benzguinols alone had no activity. Administration of three intraperitoneal (IP) doses of 20 mg/kg benzguinol A or B to mice did not result in any obvious adverse clinical or pathological evidence of acute toxicity. Importantly, mice that received three 20 mg/kg IP doses of benzguinol A or B at 4 h intervals exhibited significantly reduced bacterial loads and longer survival times than vehicle-only treated mice in a bioluminescent S. aureus murine sepsis challenge model. We conclude that the benzguinols are potential candidates for further development for specific treatment of serious bacterial infections as both stand-alone antibiotics and in combination with existing antibiotic classes.
Development and evaluation of oxaliplatin and irinotecan co-loaded liposomes for enhanced colorectal cancer therapy
Publisher: Elsevier BV
Date: 09-2016
DOI: 10.1016/J.JCONREL.2016.07.022
Abstract: Drug combinations are widely employed in chemotherapy for colorectal cancer treatment. However, traditional cocktail combination in clinic causes the uncertainty of the treatment, owing to varying pharmacokinetics of different drugs. The aim of this study was to design co-loaded liposomes to achieve the synchronised delivery and release. Oxaliplatin and irinotecan hydrochloride, as one of recommended combination schemes for the treatment of colorectal cancer in clinic, were co-loaded into the liposomes. The particle sizes of the liposomes were <200nm with uniform size distribution. In vitro release study showed that both drugs could be synchronously released from the liposomes, which means the optimized synergistic ratio of two drugs could be achieved. In vitro cellular uptake revealed that co-loaded liposomes could efficiently deliver different drugs into the same cells, indicating their potential as carriers for enhancing the cancer therapy. CLSM images of cryo-sections for in vivo co-delivery study also revealed that co-loaded liposomes had superior ability to co-deliver both the cargoes into the same tumor cells. Besides, in vivo NIRF imaging indicated that the liposomes could increase the drug accumulation in tumor compared with free drug. In vitro cytotoxicity evaluation demonstrated that co-loaded liposomes exhibited higher cytotoxicity than the mixture of single loaded liposomes in both CT-26 and HCT-116 cells. Furthermore, co-loaded liposomes also presented superior anti-tumor activity in CT-26 bearing BALB/c mice. In vivo safety assessment demonstrated that liposomes had lower toxicities than their solution formulations. These results indicated that oxaliplatin and irinotecan hydrochloride co-loaded liposomes would be an efficient formulation for improving colorectal cancer therapy with potential clinical applications.
Bioluminescent murine models of bacterial sepsis and scald wound infections for antimicrobial efficacy testing
Publisher: Public Library of Science (PLoS)
Date: 16-07-2018
Estimation of atenolol transfer into milk and infant exposure during its use in lactating women
Publisher: SAGE Publications
Date: 05-06-2018
Abstract: Atenolol lactation information is limited, and controversy exists over the safety of its use during breastfeeding. In this study, important parameters including milk-to-plasma ratio, ratio of infant plasma to maternal plasma, infant daily dosage, and relative infant dose were investigated. The findings from this study add information to existing data about atenolol transfer in human milk. This may help guide health professionals in decision making regarding the safety of beta blockers used by mothers during breastfeeding. The aims of the study were to quantify concentrations of atenolol in human plasma and milk, to evaluate atenolol pharmacokinetics in lactating women, and to investigate subsequent infant exposure to atenolol via mother’s milk. In this prospective, longitudinal observational study, participants were lactating mothers ( N = 3), 1 to 4 months postpartum, who had been taking atenolol for therapeutic reasons, and one 4-month-old breastfed infant. Eight milk s les were collected over 24 hr at different time points, together with a single blood s le from each lactating mother and the infant, and quantified using a new sensitive liquid chromatography mass spectrometry method developed for this study. Peak milk concentrations of atenolol were observed in the women at 4 hr (T max ) after oral administration. The dose-normalized maximum concentrations (C max ) of all patients were similar. The mean milk-to-plasma ratio of the patients who were taking 25 to 100 mg of atenolol was 8.57%. In the mother–infant pair study, the ratio (%) of infant plasma drug concentration to maternal plasma drug concentration observed (18.87%) was similar to the relative infant dose estimated (18.20%). The relative infant dose values (13.96%-18.20%) for all patients were within 10% to 25% of maternal dosage. Atenolol use during breastfeeding should be undertaken with some precaution. If clinically indicated, an alternate beta blocker may be preferred.
Curcumin-loaded self-nanomicellizing solid dispersion system: part I: development, optimization, characterization, and oral bioavailability
Publisher: Springer Science and Business Media LLC
Date: 29-05-2018
DOI: 10.1007/S13346-018-0543-3
Abstract: Curcumin (CUR) is considered as one of the most bioactive molecules ever discovered from nature due to its proven anti-inflammatory and antioxidant in both preclinical and clinical studies. Despite its proven safety and efficacy, the clinical translation of CUR into a useful therapeutic agent is still limited due to its poor oral bioavailability. To overcome its limitation and enhance oral bioavailability by improving its aqueous solubility, stability, and intestinal permeability, a novel CUR formulation (NCF) was developed using the self-nanomicellizing solid dispersion strategy. From the initial screening of polymers for their potential to improve the solubility and stability, Soluplus (SOL) was selected. The optimized NCF demonstrated over 20,000-fold improvement in aqueous solubility as a result of amorphization, hydrogen bonding interaction, and micellization determined using differential scanning calorimetry, X-ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, nuclear magnetic resonance, dynamic light scattering, and transmission electron microscopy. Moreover, the greater stabilizing effect in alkaline pH and light was observed. Furthermore, significant enhancement of dissolution and permeability of CUR across everted sacs of rat small intestine were noticed. Pharmacokinetic studies demonstrated that the oral bioavailability of CUR was increased 117 and 17-fold in case of NCF and physical mixture of CUR and SOL compared to CUR suspension. These results suggest NCF identified as a promising new approach for repositioning of CUR for pharmaceutical application by enhancing the oral bioavailability of CUR. The findings herein stimulate further in vivo evaluations and clinical tests of NCF.
Forced degradation of flavonol glycosides extraced from Ginkgo biloba
Publisher: Springer Science and Business Media LLC
Date: 26-06-2013
Key Considerations in Designing Oral Drug Delivery Systems for Dogs
Publisher: Elsevier BV
Date: 05-2016
DOI: 10.1016/J.XPHS.2016.03.007
Abstract: The present review discusses the pharmaceutical impact of the anatomy and physiology of the canine gastrointestinal tract to provide a comprehensive guide to the theories and challenges associated with the development of oral drug delivery systems for dogs. Novel pharmaceutical technologies applied to veterinary drugs are discussed indicating the advantages and benefits for animals. There are currently immense research and development efforts being funneled into novel canine health products. Such products are being used to overcome limitations of drugs that display site-dependent absorption or possess poor biopharmaceutical properties. Techniques that are employed to increase bioavailability of the Biopharmaceutics Classification System class II drugs are discussed in this article. Furthermore, an overview of palatable oral formulations for dog care is provided as an approach to easy administration. In vitro and in vivo evaluation and correlation of oral drug formulations in dogs are also addressed. This article assesses the outlook of canine oral drug development recognizing substantial growth forecasts of the dog care market.
Doxorubicin-Loaded Delta Inulin Conjugates for Controlled and Targeted Drug Delivery: Development, Characterization, and In Vitro Evaluation
Publisher: MDPI AG
Date: 06-11-2019
DOI: 10.3390/PHARMACEUTICS11110581
Abstract: Delta inulin, also known as microparticulate inulin (MPI), was modified by covalently attaching doxorubicin to its nanostructured surface for use as a targeted drug delivery vehicle. MPI is readily endocytosed by monocytes, macrophages, and dendritic cells and in this study, we sought to utilize this property to develop a system to target anti-cancer drugs to lymphoid organs. We investigated, therefore, whether MPI could be used as a vehicle to deliver doxorubicin selectively, thereby reducing the toxicity of this antibiotic anthracycline drug. Doxorubicin was covalently attached to the surface of MPI using an acid–labile linkage to enable pH-controlled release. The MPI-doxorubicin conjugate was characterized using FTIR and SEM, confirming covalent attachment and indicating doxorubicin coupling had no obvious impact on the physical nanostructure, integrity, and cellular uptake of the MPI particles. To simulate the stability of the MPI-doxorubicin in vivo, it was stored in artificial lysosomal fluid (ALF, pH 4.5). Although the MPI-doxorubicin particles were still visible after 165 days in ALF, 53% of glycosidic bonds in the inulin particles were hydrolyzed within 12 days in ALF, reflected by the release of free glucose into solution. By contrast, the fructosidic bonds were much more stable. Drug release studies of the MPI-doxorubicin in vitro, demonstrated a successful pH-dependent controlled release effect. Confocal laser scanning microscopy studies and flow cytometric analysis confirmed that when incubated with live cells, MPI-doxorubicin was efficiently internalized by immune cells. An assay of cell metabolic activity demonstrated that the MPI carrier alone had no toxic effects on RAW 264.7 murine monocyte/macrophage-like cells, but exhibited anti-cancer effects against HCT116 human colon cancer cells. MPI-doxorubicin had a greater anti-cancer cell effect than free doxorubicin, particularly when at lower concentrations, suggesting a drug-sparing effect. This study establishes that MPI can be successfully modified with doxorubicin for chemotherapeutic drug delivery.
Influence of Oxidation Degree on the Physicochemical Properties of Oxidized Inulin
Publisher: MDPI AG
Date: 05-2020
Abstract: This paper reports the oxidation of inulin using varying ratios of sodium periodate and the characterization of the inulin polyaldehyde. The physicochemical properties of the inulin polyaldehyde (oxidized inulin) were characterized using different techniques including 1D NMR spectroscopy, 13C Nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), differential scanning calorimetric (DSC), ultraviolet-visible spectroscopy (UV), and scanning electron microscopy (SEM). The aldehyde peak was not very visible in the FTIR, because the aldehyde functional group exists in a masked form (hemiacetal). The thermal stability of the oxidized inulin decreased with the increasing oxidation degree. The smooth spherical shape of raw inulin was destructed due to the oxidation, as confirmed by the SEM result. The 1HNMR results show some new peaks from 4.8 to 5.0 as well as around 5.63 ppm. However, no aldehyde peak was found around 9.7 ppm. This can be attributed to the hemiacetal. The reaction of oxidized inulin with tert-butyl carbazate produced a carbazone conjugate. There was clear evidence of decreased peak intensity for the proton belonging to the hemiacetal group. This clearly shows that not all of the hemiacetal group can be reverted by carbazate. In conclusion, this work provides vital information as regards changes in the physicochemical properties of the oxidized inulin, which has direct implications when considering the further utilization of this biomaterial.
Development of an extemporaneous oral liquid formulation of oxandrolone and its stability evaluation
Publisher: Elsevier BV
Date: 11-2011
DOI: 10.1016/J.BURNS.2011.06.007
Abstract: Many references exist in the literature identifying the usefulness of oxandrolone in treating muscle wasting due to various conditions including severe burns. However, there is an absence of dosage form alternatives as it is only available as tablets. The dose for children is weight based (0.1 mg/kg) which is difficult to achieve with the currently available tablets of 2.5 mg and 10 mg. The literature provides le evidence of clinical importance but little guidance on extemporaneous oral liquid formulation of oxandrolone. In order to develop and validate an extemporaneous liquid formulation, suspensions of oxandrolone were developed using locally available (New Zealand) vehicles. Combinations of these vehicles with ethanol, as advised in some articles were also tried. Assay method was developed for oxandrolone using High Performance Liquid Chromatography (HPLC) and Mass Spectroscopy (LC-MS). The formulations were evaluated for stability as per the International Conference on Harmonization (ICH) stability guidelines. They were observed for physical and chemical stability at different time points over a period of 28 days. A stable and validated liquid formulation of oxandrolone has been developed which can be made under the hospital and community pharmacy conditions. The formula utilises commercially available oxandrolone tablets, crushed and dispersed in Simple Syrup BP or Orablend(®) vehicle. The formulation has confirmed stability for 21 days and can be easily made with locally available vehicles.
Preliminary investigations into a novel, long-acting, injectable, intramuscular formulation of omeprazole in the horse
Publisher: Wiley
Date: 17-05-2017
DOI: 10.1111/EVJ.12688
Abstract: Pilot investigations have suggested that a novel, long-acting, injectable i.m. formulation of omeprazole (LA-OMEP) can induce acid suppression for up to 7 days following a single injection. To investigate the pharmacodynamics and assess the clinical efficacy of the LA-OMEP formulation. Part A comprised a pharmacodynamic study. Part B consisted of a pilot clinical trial. Part A enrolled six adult Thoroughbred horses with percutaneous gastrotomy tubes. Intragastric pH was measured for continuous 23-h periods (08.00-07.00 h) for eight consecutive days (days 0-7). A single 2.0-g dose of a 100 mg/mL LA-OMEP formulation was administered at 08.00 h on day 1. In Part B, 26 horses with squamous or glandular gastric disease were enrolled based on routine gastroscopic evaluation. Once enrolled, horses received 2.0 g of the 100 mg/mL LA-OMEP formulation by i.m. injection on days 0 and 7. Repeat gastroscopy was performed on days 14 (23 horses) or 16 (one horse). In Part A, the percentage of time during which pH was above 4 exceeded 66% for days 1-4 in all horses and days 1-7 in four of the six horses studied. In Part B, healing was observed in all 22 (100%, 95% confidence interval [CI] 89-100%) horses with squamous disease and in nine of 12 (75%, 95% CI 47-92%) horses with glandular disease. Improvement, by at least one grade, was observed in all 22 (100%, 95% CI 89-100%) horses with squamous disease and in all 12 (100%, 95% CI 81-100%) horses with glandular disease. No worsening of lesions was observed. Lesion grade decreased over time in both the squamous (P<0.0001) and glandular (P = 0.0024) mucosa. Small s le sizes. The results of the present study compare favourably with previous reports on the pharmacodynamics of omeprazole and the clinical outcomes of trials reporting response to oral omeprazole therapy.
Curcumin-loaded self-nanomicellizing solid dispersion system: part II: in vivo safety and efficacy assessment against behavior deficit in Alzheimer disease
Publisher: Springer Science and Business Media LLC
Date: 16-08-2018
DOI: 10.1007/S13346-018-0570-0
Abstract: Curcumin (CUR), a natural polyphenolic compound, is considered as one of the most potential candidates against Alzheimer disease (AD) by targeting multiple pathologies such as amyloid-beta, tau phosphorylation, and oxidative stress. Poor physicochemical profile and oral bioavailability (BA) are the major contributors to its failure in clinical trials. Lack of success in numerous drug clinical trials for the treatment of AD urges the need of repositioning of CUR. To overcome its limitation and enhance oral BA, Novel CUR Formulation (NCF) was developed using self-nanomicellizing solid dispersion strategy which displayed 117-fold enhancement in oral BA of CUR. NCF was tested using SH-SY5Y695 APP human neuroblastoma cell line against the cytotoxicity induced by copper metal ion, H
Lipid-based combinational drug delivery systems: maximizing the performance of cocktail therapy
Publisher: Elsevier
Date: 2021
Low-dose Fluoride in Postmenopausal Women: A Randomized Controlled Trial
Publisher: The Endocrine Society
Date: 06-2013
DOI: 10.1210/JC.2012-4062
Abstract: Trials of high-dose fluoride have reported increased bone formation and bone mineral density (BMD), but impaired bone mineralization and either adverse or neutral effects on fracture risk. Meta-analysis of a heterogeneous dataset of small trials suggests that daily doses of <20 mg fluoride might reduce fracture risk, but it is not known whether low doses of fluoride are safely anabolic to bone. We set out to investigate the skeletal effects of low doses of fluoride. We conducted a double-blind, placebo-controlled randomized trial over 1 year at an academic research center, in 180 postmenopausal women with osteopenia. Participants received daily treatment with tablets containing placebo, 2.5 mg fluoride, 5 mg fluoride, or 10 mg fluoride. The primary endpoint was a change in lumbar spine BMD at 1 year secondary endpoints were hip and forearm BMD, and markers of bone turnover. Safety was assessed by histomorphometric analysis of transiliac bone biopsies from a subset of participants. Compared to placebo, none of the doses of fluoride altered BMD at any site. The bone formation marker, procollagen type I N-terminal propeptide, increased significantly in the 5 mg and 10 mg fluoride groups compared to placebo (P = .04 and .005, respectively). No differences were observed between placebo and any of the fluoride groups in levels of β-C-terminal telopeptide of type I collagen. Low-dose fluoride does not induce substantial effects on surrogates of skeletal health and is unlikely to be an effective therapy for osteoporosis.
Quality, Safety and Efficacy in the ‘Off-Label’ Use of Medicines
Publisher: Bentham Science Publishers Ltd.
Date: 2007
DOI: 10.2174/157488607779315471
Abstract: Suitable dosage forms are not always available for specific patient populations and must be extemporaneously compounded. Extemporaneous preparation is the manipulation of drugs and excipients for a particular patient using traditional compounding techniques these are referred to as 'off-label' and 'unlicensed' medicines. Off-label use can include altered doses, dosage forms or indications for use. Registered medicines are produced to internationally recognized standards of Good Manufacturing Practices. Within the pharmaceutical manufacturing industry, quality, safety and efficacy are enforced by regulatory legislations. In contrast, the responsibility for acceptable standards for the compounding of 'off-label' medicines falls on the prescriber, pharmacist or hospital nurse. Studies have been conducted by researchers from Australia and throughout Europe, highlighting the frequency of off-label use for paediatrics, with one study reporting that most extemporaneous preparations (29.6%) were for drugs required to treat metabolic diseases. Risks include compounding errors, adverse reactions to ingredients and excipients, and non-validated stability of the product. Sterile compounded products, including products for ophthalmic and palliative care, carry additional risks in these vulnerable patients. This paper provides an overview of off-label medicines highlighting biopharmaceutical, quality, safety and efficacy issues important to medical and allied health professionals.
Cascade Cytosol Delivery of Dual-Sensitive Micelle-Tailored Vaccine for Enhancing Cancer Immunotherapy
Publisher: American Chemical Society (ACS)
Date: 15-10-2018
Abstract: Enhancing cytosol delivery of exogenous antigens in antigen presenting cells can improve cross-presentation and CD8+ T cell-mediated immune response. The antigen cytosol delivery speed, which has great importance on the rate of MHC class I molecules (MHC I) antigen presentation pathway and cytotoxic T lymphocytes (CTLs) induction, has not been well studied. We hypothesized that micelle-tailored vaccine with multiple cascaded lysosomal responsive capabilities could accelerate lysosomal escape and enhance cancer immunotherapy. To test our hypothesis, we created a novel micellar cancer vaccine (ovalbumin-loaded pH/redox dual-sensitive micellar vaccine, OLM-D) by cleavable conjugation of an antigen with house-made hiphilic poly(l-histidine)-poly(ethylene glycol) (PLH-PEG) in current study. OLM-D was supposed to achieve cascade cytosol delivery of ovalbumin through three steps in terms of (i) initial redox triggered ovalbumin release, (ii) promoted proton inflow and micelle disassembly, and (iii) speeded proton sponge effect and lysosome bulging/broke. Redox-sensitive antigen release and consequently accelerative OLM-D disassembly were confirmed by sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS-PAGE), transmission electronic microscopy (TEM), particle sizes, zeta potentials, and in vitro Ova release evaluation. The speeded cytosol delivery of ovalbumin was visualized under a confocal laser scanning microscope (CLSM). The ability of OLM-D to increase the MHC I molecule combination rate and antigen cross-presentation efficiency was identified by antigen presentation assay and maturation assay in bone marrow-derived dendritic cells (BMDCs). In vivo, the capability of OLM-D to accumulate in draining lymph nodes (LNs) after injection was visualized by real-time near infrared fluorescence imaging (NIRF) and the distribution order in different LNs was first observed (a, d, c, b). Enhanced cancer immunity of OLM-D was confirmed by increased CD3+CD8+ T cell quantity, CD3+CD8+25D11.6+ T cells quantity, and IFN-γ, IL-2 secretion post subcutaneous or intraperitoneal injection ( p < 0.05). Taken together, our results indicated that OLM-D provided a promising cascade cytosol delivery strategy, which held great potential to guide further design of nano-particulate cancer vaccines for efficient cancer immunotherapy.
Formulation development and dissolution rate enhancement of efavirenz by solid dispersion systems
Publisher: OMICS Publishing Group
Date: 2013
Within or Without You? A Perspective Comparing In Situ and Ex Situ Tissue Engineering Strategies for Articular Cartilage Repair
Publisher: Wiley
Date: 22-11-2022
Abstract: Human articular cartilage has a poor ability to self‐repair, meaning small injuries often lead to osteoarthritis, a painful and debilitating condition which is a major contributor to the global burden of disease. Existing clinical strategies generally do not regenerate hyaline type cartilage, motivating research toward tissue engineering solutions. Prospective cartilage tissue engineering therapies can be placed into two broad categories: i) Ex situ strategies, where cartilage tissue constructs are engineered in the lab prior to implantation and ii) in situ strategies, where cells and/or a bioscaffold are delivered to the defect site to stimulate chondral repair directly. While commonalities exist between these two approaches, the core point of distinction—whether chondrogenesis primarily occurs “within” or “without” (outside) the body—can dictate many aspects of the treatment. This difference influences decisions around cell selection, the biomaterials formulation and the surgical implantation procedure, the processes of tissue integration and maturation, as well as, the prospects for regulatory clearance and clinical translation. Here, ex situ and in situ cartilage engineering strategies are compared: Highlighting their respective challenges, opportunities, and prospects on their translational pathways toward long term human cartilage repair.
Development of a novel probiotic delivery system based on microencapsulation with protectants
Publisher: Springer Science and Business Media LLC
Date: 06-10-2011
DOI: 10.1007/S00253-011-3609-4
Abstract: The establishment of the health-promoting benefits of probiotics is challenged by the antimicrobial bio-barriers throughout the host's gastrointestinal (GI) tract after oral administration. Although microencapsulation has been frequently utilised to enhance the delivery of probiotics, microcapsules of sub-100 μm were found to be ineffective and therefore questioned as an effective delivery vehicle for viable probiotics despite the sensory advantage. In this study, four probiotics strains were encapsulated in chitosan-coated alginate microcapsules of sub-100 μm. Only a minor protective effect was observed from this original type of microcapsule. In order to enhance the survival of these probiotics, sucrose, a metabolisable sugar, and lecithin vesicles were added to the wall material. Both of the ingredients could be readily encapsulated with the probiotics, and protected them from stresses in the simulated GI fluids. The metabolisable sugar effectively increased the survival of the probiotics in gastric acid, mainly through energizing the membrane-bound F1F0-ATPases. The lecithin vesicles proved to alleviate the bile salt stress, and hence notably reduced the viability loss at the elevated bile salt concentrations. Overall, three out of the total four probiotics in the reinforced sub-100 μm microencapsules could significantly survive through an 8-h sequential treatment of the simulated GI fluids, giving less than 1-log drop in viable count. The most vulnerable strain of bifidobacteria also yielded a viability increase of 3-logs from this protection. In conclusion, the sub-100 μm microcapsules can be a useful vehicle for the delivery of probiotics, as long as suitable protectants are incorporated in the wall matrix.
Repurposing Ionophores as novel antimicrobial agents for the treatment of bovine mastitis caused by Gram-positive pathogens
Publisher: Wiley
Date: 04-07-2018
DOI: 10.1111/JVP.12674
Abstract: Increasing reports of multidrug-resistant bacterial infections in animals has created a need for novel antimicrobial agents that do not promote cross-resistance to critically important antimicrobial classes used in human medicine. In response to the recent emergence of antimicrobial resistance in several bovine mastitis pathogens, in vitro antimicrobial susceptibility was determined for four polyether ionophores (lasalocid, monensin, narasin and salinomycin) against Staphylococcus spp. and Streptococcus spp. isolated from clinical cases. In addition, erythrocyte haemolysis and WST-1 cell proliferation assays were used to assess in vitro mammalian cell cytotoxicity and biofilm susceptibility testing was performed using the minimum biofilm eradication concentration (MBEC™) biofilm assay. Lasalocid, monensin, narasin and salinomycin exhibited bacteriostatic antimicrobial activity against all pathogens tested, including methicillin-resistant staphylococci, with MIC
Development of a novel chromatographic method for concurrent determination of 5-fluorouracil and cisplatin: validation, greenness evaluation, and application on drug-eluting film
Publisher: Elsevier BV
Date: 09-2021
Preparation and Characterization of Oxidized Inulin Hydrogel for Controlled Drug Delivery
Publisher: MDPI AG
Date: 22-07-2019
DOI: 10.3390/PHARMACEUTICS11070356
Abstract: Inulin-based hydrogels are useful carriers for the delivery of drugs in the colon-targeted system and in other biomedical applications. In this project, inulin hydrogels were fabricated by crosslinking oxidized inulin with adipic acid dihydrazide (AAD) without the use of a catalyst or initiator. The physicochemical properties of the obtained hydrogels were further characterized using different techniques, such as swelling experiments, in vitro drug release, degradation, and biocompatibility tests. The crosslinking was confirmed with Fourier transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), and differential scanning calorimetry (DSC). In vitro releases of 5-fluorouracil (5FU) from the various inulin hydrogels was enhanced in acidic conditions (pH 5) compared with physiological pH (pH 7.4). In addition, blank gels did not show any appreciable cytotoxicity, whereas 5FU-loaded hydrogels demonstrated efficacy against HCT116 colon cancer cells, which further confirms the potential use of these delivery platforms for direct targeting of 5-FU to the colon.
Chemistry and pharmacology of the citrus bioflavonoid hesperidin
Publisher: Wiley
Date: 23-10-2001
DOI: 10.1002/PTR.1074
Abstract: Hesperidin, a bioflavonoid, is an abundant and inexpensive by-product of Citrus cultivation. A deficiency of this substance in the diet has been linked with abnormal capillary leakiness as well as pain in the extremities causing aches, weakness and night leg cr s. No signs of toxicity have been observed with the normal intake of hesperidin or related compounds. Both hesperidin and its aglycone hesperetin have been reported to possess a wide range of pharmacological properties. This paper reviews various aspects of hesperidin and its related compounds, including their occurrence, physical and chemical properties, analysis, pharmacokinetics, safety and toxicity and the marketed products available. A special emphasis has been laid on the pharmacological properties and medicinal uses of these compounds.
Functionalized Mesoporous Silica Nanoparticles as Delivery Systems for Doxorubicin: Drug Loading and Release
Publisher: MDPI AG
Date: 30-06-2021
DOI: 10.3390/APP11136121
Abstract: Functionalized nanoparticles have played a major role in the field of targeted therapy, owing to their ability to control the release and for the selective delivery of entrapped materials to tumours. In this work, we described the loading capacity and in vitro release kinetics of mesoporous silica nanoparticles (MSNs), functionalized with Poly-L-Histidine and Tamoxifen. The model drug Doxorubicin (DOX) was successfully encapsulated into MSN-based systems, using the technique of solvent immersion. A post-surface grafting loading method was investigated on functionalized systems, with DOX loading content determined using HPLC. Dialysis bag diffusion was employed to investigate the release kinetics of DOX-loaded-systems at pH 7.4 and 5. The amount of DOX released from native MSNs systems over a 72 h period at pH 5 was approximately 40% and at pH 7.4 ≈ 30%. A moderate pH dependent release behaviour was observed with both our functionalized systems: DOX@MSN-PLH and DOX@MSN-PLH-TAM with approximately 5% of DOX released from DOX@MSN-PLH-TAM at pH 7.4 and about 9% released at pH 7.4 over 72 h. The maximal cumulated release of DOX molecules from DOX@MSN-PLH after 72 h was ≈18% at pH 7.4 and ≈23% at pH 5, respectively. The outcome of this work offers a promising contribution towards building future stimuli-responsive nano-drug delivery systems.
Stability evaluation of an extemporaneously compounded carbimazole oral suspension
Publisher: Wiley
Date: 08-07-2020
DOI: 10.1002/JPPR.1631
Herbal medicines for sexually transmitted diseases and AIDS
Publisher: Elsevier BV
Date: 04-2002
DOI: 10.1016/S0378-8741(02)00009-0
Abstract: Sexually transmitted diseases (STDs) and acquired immunodeficiency syndrome (AIDS) are gaining significant importance at present due to rapid spread of the diseases, high cost of treatment, and the increased risk of transmission of other STDs and AIDS. Current therapies available for symptomatic treatment of STDs and AIDS are quite expensive beyond the reach of common man and are associated with emergence of drug resistance. Many patients of STDs and AIDS are seeking help from alternative systems of medicines such as Unani, Chinese, Ayurvedic, naturopathy, and homeopathy. Since a long time, medicinal plants have been used for the treatment of many infectious diseases without any scientific evidence. At present there is more emphasis on determining the scientific evidence and rationalization of the use of these preparations. Research is in progress to identify plants and their active principles possessing activity against sexually transmitted pathogens including human immunodeficiency virus (HIV) with an objective of providing an effective approach for prevention of transmission and treatment of these diseases. In the present review, plants reported to possess activity or used in traditional systems of medicine for prevention and treatment of STDs including AIDS, herbal formulations for vaginal application, and topical microbicides from herbal origin, have been discussed.
The Management of Parkinson’s Disease: An Overview of the Current Advancements in Drug Delivery Systems
Publisher: MDPI AG
Date: 15-05-2023
DOI: 10.3390/PHARMACEUTICS15051503
Abstract: Parkinson’s disease (PD) has significantly affected a large proportion of the elderly population worldwide. According to the World Health Organization, approximately 8.5 million people worldwide are living with PD. In the United States, an estimated one million people are living with PD, with approximately 60,000 new cases diagnosed every year. Conventional therapies available for Parkinson’s disease are associated with limitations such as the wearing-off effect, on-off period, episodes of motor freezing, and dyskinesia. In this review, a comprehensive overview of the latest advances in DDSs used to reduce the limitations of current therapies will be presented, and both their promising features and drawbacks will be discussed. We are also particularly interested in the technical properties, mechanism, and release patterns of incorporated drugs, as well as nanoscale delivery strategies to overcome the blood–brain barrier.
Drug development in NZ: can a country be a cluster?
Publisher: Wiley
Date: 28-11-2011
DOI: 10.1002/DDR.20489
Enhancement of docetaxel solubility using binary and ternary solid dispersion systems
Publisher: Informa UK Limited
Date: 04-09-2015
DOI: 10.3109/03639045.2015.1014818
Abstract: Poor biopharmaceutical properties and toxicities associated with the intravenous formulation of docetaxel (DTX) necessitate the exploration of an alternate oral route of delivery. This study aims at enhancing the solubility of poorly soluble drug, DTX with the help of solid dispersion (SD) technique. DTX SDs were formulated with selected solubilizers, including Kollidon 12PF, Lutrol F68, Soluplus and Hydroxypropyl-β-cyclodextrin in different weight ratios. Freeze-drying method was used to prepare the binary and ternary SDs. Kinetic solubility of the SDs was evaluated in order to select best DTX-solubilizer combination. Best performing combination was then characterized using differential scanning calorimeter (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). Among all SDs tested, Soluplus outperformed all the excipients at equivalent weight ratio. Binary SD of DTX and Soluplus (1:10) resulted in the highest improvement in solubility (362.93 ± 11.01 µg/mL). This is approximately a 93-fold increment as compared to the solubility of crystalline DTX (3.9 ± 0.2 µg/mL). This exceptional performance can be attributed to solid-state transformation as well as micellization. Among all the excipients tested, Soluplus dispersion is the most promising candidate for oral formulation development.
Efficient co-delivery of immiscible hydrophilic/hydrophobic chemotherapeutics by lipid emulsions for improved treatment of cancer
Publisher: Informa UK Limited
Date: 04-2017
DOI: 10.2147/IJN.S129091
Self-nanomicellizing solid dispersion of edaravone: part II: in vivo assessment of efficacy against behavior deficits and safety in Alzheimer's disease model
Publisher: Informa UK Limited
Date: 07-2018
DOI: 10.2147/DDDT.S161944
Nanotechnology and narasin: a powerful combination against acne
Publisher: Royal Society of Chemistry (RSC)
Date: 2023
DOI: 10.1039/D3NR01789C
Abstract: We have unleashed the potential of NAR and its nanoformulation against acne infections. The results of the ex vivo skin deposition study demonstrate the effectiveness of the developed nano gel as a targeted topical therapy for acne.
Mesoporous Silica Nanoparticles: A Comprehensive Review on Synthesis and Recent Advances
Publisher: MDPI AG
Date: 06-08-2018
DOI: 10.3390/PHARMACEUTICS10030118
Abstract: Recent advancements in drug delivery technologies utilizing a variety of carriers have resulted in a path-breaking revolution in the approach towards diagnosis and therapy alike in the current times. Need for materials with high thermal, chemical and mechanical properties have led to the development of mesoporous silica nanoparticles (MSNs). These ordered porous materials have garnered immense attention as drug carriers owing to their distinctive features over the others. They can be synthesized using a relatively simple process, thus making it cost effective. Moreover, by controlling the parameters during the synthesis the morphology, pore size and volume and particle size can be transformed accordingly. Over the last few years, a rapid increase in research on MSNs as drug carriers for the treatment of various diseases has been observed indicating its potential benefits in drug delivery. Their widespread application for the loading of small molecules as well as macromolecules such as proteins, siRNA and so forth, has made it a versatile carrier. In the recent times, researchers have sorted to several modifications in the framework of MSNs to explore its potential in drug resistant chemotherapy, antimicrobial therapy. In this review, we have discussed the synthesis of these multitalented nanoparticles and the factors influencing the size and morphology of this wonder carrier. The second part of this review emphasizes on the applications and the advances made in the MSNs to broaden the spectrum of its use especially in the field of biomedicine. We have also touched upon the lacunae in the thorough understanding of its interaction with a biological system which poses a major hurdle in the passage of this carrier to the clinical level. In the final part of this review, we have discussed some of the major patents filed in the field of MSNs for therapeutic purpose.
Development, implementation and evaluation of an innovative, project-based assignment for pharmacy and pharmaceutical science students, relating to advanced drug delivery systems
Publisher: Elsevier BV
Date: 05-2019
Three-Dimensional Printing of Curcumin-Loaded Biodegradable and Flexible Scaffold for Intracranial Therapy of Glioblastoma Multiforme
Publisher: MDPI AG
Date: 31-03-2021
DOI: 10.3390/PHARMACEUTICS13040471
Abstract: A novel drug delivery system preventing Glioblastoma multiforme (GBM) recurrence after resection surgery is imperatively required to overcome the mechanical limitation of the current local drug delivery system and to offer personalised treatment options for GBM patients. In this study, 3D printed biodegradable flexible porous scaffolds were developed via Fused Deposition Modelling (FDM) three-dimensional (3D) printing technology for the local delivery of curcumin. The flexible porous scaffolds were 3D printed with various geometries containing 1, 3, 5, and 7% (w/w) of curcumin, respectively, using curcumin-loaded polycaprolactone (PCL) filaments. The scaffolds were characterised by a series of characterisation studies and in vitro studies were also performed including drug release study, scaffold degradation study, and cytotoxicity study. The curcumin-loaded PCL scaffolds displayed versatile spatiotemporal characteristics. The polymeric scaffolds obtained great mechanical flexibility with a low tensile modulus of less than 2 MPa, and 4 to 7-fold ultimate tensile strain, which can avoid the mechanical mismatch problem of commercially available GLIADEL wafer with a further improvement in surgical margin coverage. In vitro release profiles have demonstrated the sustained release patterns of curcumin with adjustable release amounts and durations up to 77 h. MTT study has demonstrated the great cytotoxic effect of curcumin-loaded scaffolds against the U87 human GBM cell line. Therefore, 3D printed curcumin-loaded scaffold has great promise to provide better GBM treatment options with its mechanical flexibility and customisability to match in idual needs, preventing post-surgery GBM recurrence and eventually prolonging the life expectancy of GBM patients.
Development and Optimization of Imiquimod-Loaded Nanostructured Lipid Carriers Using a Hybrid Design of Experiments Approach
Publisher: Informa UK Limited
Date: 02-2023
DOI: 10.2147/IJN.S400610
Development and evaluation of osmotically controlled oral drug delivery system of glipizide
Publisher: Elsevier BV
Date: 05-2004
Development and Validation of a Novel Tool for Assessing the Environmental Impact of 3D Printing Technologies: A Pharmaceutical Perspective
Publisher: MDPI AG
Date: 03-03-2022
DOI: 10.3390/PHARMACEUTICS14050933
Abstract: Technological advancements have created infinite opportunities and rendered our life easier at several fronts. Nonetheless, the environment has suffered the aftermaths of modernization. Ironically, the pharmaceutical industry was found to be a significant contributor to environmental deterioration. To tackle this issue, continuous eco-evaluation of newly introduced technologies is crucial. Three-dimensional printing (3DP) is rapidly establishing its routes in different industries. Interestingly, 3DP is revolutionising the production of pharmaceuticals and is regarded as a promising approach for the fabrication of patient-centric formulations. Despite the increasing applications in the pharmaceutical field, tools that evaluate the environmental impacts of 3DP are lacking. Energy and solvent consumption, waste generation, and disposal are the main associated factors that present major concerns. For the first time, we are proposing a quantitative tool, the index of Greenness Assessment of Printed Pharmaceuticals (iGAPP), that evaluates the greenness of the different 3DP technologies used in the pharmaceutical industry. The tool provides a colour-coded pictogram and a numerical score indicating the overall greenness of the employed printing method. Validation was performed by constructing the greenness profile of selected formulations produced using the different 3DP techniques. This tool is simple to use and indicates the greenness level of the procedures involved, thereby creating an opportunity to modify the processes for more sustainable practices.
Chitosan-glucuronic acid conjugate coated mesoporous silica nanoparticles: a smart pH-responsive and receptor-targeted system for colorectal cancer therapy
Publisher: Elsevier BV
Date: 06-2021
All that glitters is not gold: Do movie quality and contents influence box-office revenues in China?
Publisher: Elsevier BV
Date: 03-2022
Self-nanomicellizing solid dispersion of edaravone: part I - oral bioavailability improvement
Publisher: Informa UK Limited
Date: 07-2018
DOI: 10.2147/DDDT.S161940
Development of Intramammary Drug Delivery Systems: Novel In Vitro Release Method
Publisher: Elsevier BV
Date: 03-2017
DOI: 10.1016/J.XPHS.2016.11.012
Abstract: The aim of this study was to develop an in vitro release model for intramammary drug delivery system (IMDS) evaluation. This study was the first to establish an in vitro-in vivo correlation with investigation of an IMDS containing lasalocid. Three different methods including the standard United States Pharmacopeia dissolution method with apparatus 2, a modified United States Pharmacopeia method using a dialysis bag, or a specifically designed enhancer cell system, were assessed for the release study. Full cream milk and water were selected as the release media. In vivo evaluation was carried out by administering lasalocid IMDS into the udder of lactating Holstein dairy cows. Milk s les were collected and analyzed at selected time points after treatment. Dissolution data were fitted to various kinetic models. The results indicated that the release rate of lasalocid from IMDS was controlled by factors other than diffusion, which could include the sedimentation of lasalocid to the interface and the wetting of lasalocid particles by water at the interface of oil in the formulation and release media. The results obtained in vivo and in vitro were consistent. The in vitro assessment supports formulation design for early stage development and potentially for in vivo performance analysis.
New Zealand’s Drug Development Industry
Publisher: MDPI AG
Date: 13-09-2013
Engineering Stent Based Delivery System for Esophageal Cancer Using Docetaxel
Publisher: American Chemical Society (ACS)
Date: 22-05-2015
DOI: 10.1021/MP500851U
Abstract: Esophageal cancer patients are often diagnosed as "advanced" cases. These patients are subjected to palliative stenting using self-expanding metallic stents (SEMS) to maintain oral alimentation. Unfortunately, SEMS get reoccluded due to tumor growth, in and over the stent struts. To investigate potential solutions to this problem, docetaxel (DTX) delivery films were prepared using PurSil AL 20 (PUS), which can be used as a covering material for the SEMS. Drug-polymer miscibility and interactions were studied. Bilayer films were prepared by adhering the blank film to the DTX loaded film in order to maintain the unidirectional delivery to the esophagus. In vitro release and the local DTX delivery were studied using in vitro permeation experiments. It was found that DTX and PUS were physically and chemically compatible. The bilayer films exhibited sustained release (>30 days) and minimal DTX permeation through esophageal tissues in vitro. The rate-determining step for the DTX delivery was calculated. It was found that >0.9 fraction of rate control lies with the esophageal tissues, suggesting that DTX delivery can be sustained for longer periods compared to the in vitro release observed. Thus, the bilayer films can be developed as a localized sustained delivery system in combination with the stent.
Quality-by-Design Approach for the Development of Nano-Sized Tea Tree Oil Formulation-Impregnated Biocompatible Gel with Antimicrobial Properties
Publisher: MDPI AG
Date: 13-11-2020
DOI: 10.3390/PHARMACEUTICS12111091
Abstract: Despite the promising properties of tea tree oil (TTO) as potential therapeutics for several superficial skin conditions, certain limitations such as physical instability and skin irritation have restricted its widespread use. This study focuses on developing a rationally designed lipid-based nanoformulation (TTO-LNF) in accordance with the US Food and Drug Administration standard using a well-recognized quality-by-design (QbD) approach. Using a mixture experimental design, TTO-LNF has been optimized with 5% TTO, 10% surfactant, 5% co-surfactant, and 80% water, which showed a 14.4 ± 4.4 nm droplet size and 0.03 ± 0.01 polydispersity index (PDI). To ease the topical administration, the TTO-LNF gel formulation was further developed using xanthan gum to achieve the desired viscosity and form a gel. The in vitro antibacterial tests of TTO-LNF showed promising inhibitory effects toward both Gram-negative and Gram-positive bacteria. In fact, a complete growth inhibition of S. epidermidis was observed when exposed to TTO-LNF and TTO-LNF gel for 24 h, showing better activity than antibiotic kanamycin (25 µg/mL). Additionally, the in vitro release study showed a sustained release profile with a 50% release in 24 h, which could be beneficial to reduce the toxicity and thereby improve the therapeutic efficacy for long-acting applications. Furthermore, the formulations were remarkably stable at 40 °C/75% Relative humidity (RH) for at least 4 weeks. Therefore, this study presents a promising strategy to develop a biocompatible and stable formulation that can be used for the topical treatment of skin infections.
Review of polysaccharide particle-based functional drug delivery
Publisher: Elsevier BV
Date: 10-2019
The scope and potential of vaginal drug delivery
Publisher: Elsevier BV
Date: 10-2000
DOI: 10.1016/S1461-5347(00)00296-0
Abstract: The vagina, in addition to being a genital organ with functions related to conception, serves as a potential route for drug administration. Mainly used for local action in the cervico-vaginal region, it has the potential of delivering drugs for systemic effects and uterine targeting. Currently available vaginal dosage forms have several limitations, necessitating the need to develop novel drug delivery systems. In addition, consideration of the regulatory aspects and consumer preferences for vaginal formulations is also required in the early stages of development.
Extemporaneous compounding in New Zealand hospitals
Publisher: Oxford University Press (OUP)
Date: 06-2007
Abstract: The skill to compound non-sterile products is one of the seven competencies required of entry-level pharmacists for registration with the New Zealand Pharmacy Council. The need for extemporaneous compounding skills has been questioned in other countries, as it is argued that the skill is not often required in modern pharmacy settings. The aim of the current study was to determine the scope and frequency of extemporaneous compounding in New Zealand hospitals Retrospective data were collected from eight large hospitals where extemporaneous compounded is regularly undertaken, for the period June 1, 2004 to December 31, 2004. Data were retrieved from compounding logbooks and batch sheets in hospital dispensaries. Data were collected from the north and south islands of the country. There are 32 hospitals of various sizes in New Zealand but extemporaneous compounding is not undertaken at all of them due to staff shortages or lack of demand. There were 2015 products compounded over the seven-month period, with an average of 251.9 per month. Suspensions were the most frequently compounded oral dosage form. Omeprazole suspension was the most frequently compounded extemporaneous product. Nearly one-third of the compounded products were for beta-blockers. Creams, ointments and non-oral solutions were the most common topical compounded products. Pharmacists perform a broad range of extemporaneous compounding, and the skill of compounding is thus an essential competency for all hospital pharmacists.
Formulation and pharmacokinetic evaluation of an asulacrine nanocrystalline suspension for intravenous delivery
Publisher: Elsevier BV
Date: 02-2009
DOI: 10.1016/J.IJPHARM.2008.09.022
Abstract: Asulacrine (ASL) is an inhibitor of topoisomerase II, which has shown potential against breast and lung cancer. It is a poorly water soluble drug. To allow intravenous (i.v.) administration, ASL was formulated as a nanocrystalline suspension by high pressure homogenization. The nanosuspension was lyophilized to obtain the dry ASL nanoparticles (average size, 133+/-20nm), which enhanced both the physical and chemical stability of the ASL nanoparticles. ASL dissolution and saturation solubility were enhanced by the nanosuspension. Differential scanning calorimetry and X-ray diffraction analysis showed that the crystallinity of the ASL was preserved during the high pressure homogenization process. The pharmacokinetics and tissue distribution of ASL administered either as a nanosuspension or as a solution were compared after i.v. administration to mice. In plasma, ASL nanosuspension exhibited a significantly (P<0.01) reduced C(max) (12.2+/-1.3microg ml(-1)vs 18.3+/-1.0microg ml(-1)) and AUC(0-infinity) (18.7+/-0.5microg ml(-1)h vs 46.4+/-2.6microg ml(-1)h), and a significantly (P<0.01) greater volume of distribution (15.5+/-0.6lkg(-1)vs 2.5+/-0.1lkg(-1)), clearance (1.6+/-0.04lh(-1)kg(-1)vs 0.6+/-0.04lh(-1)kg(-1)) and elimination half-life (6.1+/-0.1h vs 2.7+/-0.2h) compared to the ASL solution. In contrast, the ASL nanosuspension resulted in a significantly greater AUC(0-infinity) in liver, lung and kidney (all P<0.01), but not in heart.
Drug development and research in New Zealand: policies affecting the industry
Publisher: Wiley
Date: 27-07-2011
DOI: 10.1002/DDR.20460
In vitroActivity of Robenidine Analog NCL195 in Combination With Outer Membrane Permeabilizers Against Gram-Negative Bacterial Pathogens and Impact on Systemic Gram-Positive Bacterial Infection in Mice
Publisher: Frontiers Media SA
Date: 04-08-2020
Development and validation of bioanalytical method for the determination of asulacrine in plasma by liquid chromatography
Publisher: Elsevier BV
Date: 2008
DOI: 10.1016/J.JPBA.2007.09.025
Abstract: Asulacrine (9-[(2-methoxy-4-methylsulphonylamino)phenylamino]-N,5-dimethyl-4-acridinecarboxamide), an analogue of the antileukaemia drug amsacrine, has high antitumour activity in mice and has also shown clinical activity. A simple method is described for the quantitation of asulacrine in plasma by liquid chromatography. Chromatographic separation was achieved on a reversed phase C 18 column (250 mm x 4.6mm, particle size 5 microm, Gemini) using isocratic elution (acetonitrile and 0.01 M sodium acetate buffer pH 4.0, 45/55, v/v) at a flow rate of 1 ml/min. Asulacrine and internal standard (the ethylsulphonanilide analogue) were measured using UV detection at 254 nm. The total chromatographic run-time was 8 min with asulacrine and internal standard eluting at approximately 4.7 and approximately 6.5 min, respectively. Limit of quantification was 0.1microg/ml. The linearity range of the method was 0.1-10 microg/ml (r2=0.9995). Mean recoveries from plasma were 100-105%. Intra-batch and inter-batch precision was 7.1 and 7.8%, respectively, and intra-batch and inter-batch accuracy (relative error) was 4.9 and 8.4%, respectively (n=8 in all cases). The bench top, freeze thaw, short-term storage and stock solution stability evaluation indicated no evidence of degradation of asulacrine. The validated method is simple, selective and rapid and can be used for pharmacokinetic studies in mice.
Folic acid-grafted bovine serum albumin decorated graphene oxide: an efficient drug carrier for targeted cancer therapy
Publisher: Elsevier BV
Date: 03-2017
DOI: 10.1016/J.JCIS.2016.11.097
Abstract: Targeting drug carrier systems based on graphene oxide (GO) are of great interest, since it can selectively deliver anticancer drugs to tumor cells, and enhance therapeutic activities with minimized side effects. However, direct grafting target molecules on GO usually results in aggregation of physiological fluid, limiting its biomedical applications. Here, we propose a new strategy to construct targeting GO drug carrier using folic acid grafted bovine serum albumin (FA-BSA) as both the stabilizer and targeting agent. FA-BSA decorated graphene oxide-based nanocomposite (FA-BSA/GO) was fabricated by the physical adsorption of FA-BSA on GO, which was developed as a targeting drug delivery carrier. FA-BSA/GO as the drug carrier was associated with anticancer drug doxorubicin (DOX) through π-π and hydrogen-bond interactions, resulting in high drug loading (up to 437.43μgDOX/mgFA-BSA/GO). FA-BSA/GO/DOX systems demonstrated pH responsive and sustained drug release. The hemolysis ratio of FA-BSA/GO was less than 5%, demonstrating its safety as drug carrier for intravenous injection. Moreover, in vitro cell cytotoxicity and cellular uptake analysis suggested that the constructed FA-BSA/GO/DOX nanohybrids could significantly enhance the anticancer activity. The present work has confirmed the potential for fabrication of highly stable and dispersible GO-based targeting delivery systems for efficient cancer therapy.
Three-Dimensional Printing for Cancer Applications: Research Landscape and Technologies
Publisher: MDPI AG
Date: 10-08-2021
DOI: 10.3390/PH14080787
Abstract: As a variety of novel technologies, 3D printing has been considerably applied in the field of health care, including cancer treatment. With its fast prototyping nature, 3D printing could transform basic oncology discoveries to clinical use quickly, speed up and even revolutionise the whole drug discovery and development process. This literature review provides insight into the up-to-date applications of 3D printing on cancer research and treatment, from fundamental research and drug discovery to drug development and clinical applications. These include 3D printing of anticancer pharmaceutics, 3D-bioprinted cancer cell models and customised nonbiological medical devices. Finally, the challenges of 3D printing for cancer applications are elaborated, and the future of 3D-printed medical applications is envisioned.
Design, development and evaluation of Resveratrol transdermal patches for breast cancer therapy
Publisher: Elsevier BV
Date: 02-2022
Comparison of extraction procedures on the immunocontraceptive activity of neem seed extracts
Publisher: Elsevier BV
Date: 10-1994
DOI: 10.1016/0378-8741(94)90073-6
Abstract: Azadirachta indica (Neem) seed extracts are known to activate the local cell-mediated immune reactions after a single intrauterine administration, leading to a long term reversible block of fertility. In order to identify and characterize the active fraction responsible for this activity, neem seeds were extracted by both mechanical expression and solvent extraction using a range of polar to non-polar solvents which yielded 3 broad fractions. The mechanically expressed oil was fractionated using different approaches and studied for antifertility activity. The hexane extract and a corresponding column fraction showed potent and reproducible antifertility activity. Other fractions were less stable with regard to reproducibility of effects and composition. It is our conclusion that for subsequent fractionation to reach the last active fraction, the hexane extract is the most useful starting material.
Survey of vaginal formulations available on the Indian market: Physicochemical characterization of selected products
Publisher: Springer Science and Business Media LLC
Date: 06-2002
Advanced Strategies of Drug Delivery via Oral, Topical, and Parenteral Administration Routes: Where do Equine Medications Stand?
Publisher: MDPI AG
Date: 04-01-2023
DOI: 10.3390/PHARMACEUTICS15010186
Abstract: While the global market for veterinary products has been expanding rapidly, there is still a lack of specialist knowledge of equine pharmaceutics. In many cases, the basic structure of the gastrointestinal tract (GIT) and integumentary system of the horse shares similarities with those of humans. Generally, the dosage form developed for humans can be repurposed to deliver equine medications however, due to physiological variation, the therapeutic outcomes can be unpredictable. This is an area that requires more research, as there is a clear deficiency in literature precedence on drug delivery specifically for horses. Through a careful evaluation of equine anatomy and physiology, novel drug delivery systems (NDDSs) can be developed to adequately address many of the medical ailments of the horse. In addition to this, there are key considerations when delivering oral, topical, and parenteral drugs to horses, deriving from age and species variation. More importantly, NDDSs can enhance the duration of action of active drugs in animals, significantly improving owner compliance and ultimately, enhancing the convenience of product administration. To address the knowledge gap in equine pharmaceutical formulations, this paper begins with a summary of the anatomy and physiology of the equine gastrointestinal, integumentary, and circulatory systems. A detailed discussion of potential dosage-form related issues affecting horses, and how they can be overcome by employing NDDSs is presented.
Transfer of rosuvastatin into breast milk: liquid chromatography–mass spectrometry methodology and clinical recommendations
Publisher: Informa UK Limited
Date: 10-2018
DOI: 10.2147/DDDT.S184053
An Overview on Chemical Derivatization and Stability Aspects of Selected Avermectin Derivatives
Publisher: Pharmaceutical Society of Japan
Date: 2012
Abstract: Naturally occurring avermectins (AVMs) and its derivatives are potent endectocide compounds, well-known for their novel mode of action against a broad range of nematode and anthropod animal parasites. In this review, chemical and pharmaceutical aspects of AVM derivatives are described including stability, synthetic and purification processes, impurities and degradation pathways, and subsequent suggestions are made to improve the chemical stability. It has been found out that unique structure of AVM molecules and presence of labile groups facilitated the derivatization of AVM into various compounds showing strong anthelmintic activity. However, the same unique structure is also responsible for labile nature related to sensitive stability profile of molecules. AVMs are found to be unstable in acidic and alkaline conditions. In addition, these compounds are sensitive to strong light, and subsequently presence of photo-isomer in animals treated topically with AVM product is well known. The pharmacoepial recommendations for addition of antioxidant into drug substance, as well as its products, arises from the fact that AVM are very sensitive to oxidation. Formations of solvates, salts, epoxides, reduction of double bonds and developing liquid formulation around pH 6.2, were some chemical approaches used to retard the degradation in AVM. This coherent review will contribute towards the better understanding of the correlation of chemical processes, stability profile and biological activity therefore, it will help to design the shelf-life stable formulations containing AVMs.
Intrinsically Conducting Polymer Platforms for Electrochemically Controlled Drug Delivery
Publisher: Springer Berlin Heidelberg
Date: 2010
DOI: 10.1007/8415_2010_49
Development of a Novel Vaginal Drug Delivery System to Control Time of Farrowing and Allow Supervision of Piglet Delivery
Publisher: MDPI AG
Date: 31-01-2022
DOI: 10.3390/PHARMACEUTICS14020340
Abstract: The swine industry has evolved significantly in the recent decades, but this has come at considerable expense to piglet survival. Breeding sows for greater prolificacy has been accompanied by a greater proportion of piglets being born underweight, of lower vigor, and higher susceptibility to early mortality. Inducing sows to farrow during working hours has the potential to increase piglet survivability, but non-therapeutic injectable products are often discouraged on farms. We aimed to design and develop a novel vaginal drug delivery system (NVDDS) that could reliably trigger luteolysis and induce parturition. To achieve this, two vaginal tablets containing the luteolytic agent cloprostenol were formulated to be inserted together: one would release constituents immediately on insertion (immediate release IR) and the other would release cloprostenol in a controlled manner (controlled release CR). The two formulations (IR and CR) were evaluated for drug release, swelling and bio-adhesion in conditions simulating the sow vaginal environment. The IR tablet released the drug completely for 5 min whereas the CR tablet took 5 h to release 50% of the drug. Furthermore, the release kinetics were evaluated by fitting the dissolution profiles into different mathematical models. Both IR and CR tablets were best fitted by the Makoid–Banakar model which assumes release by summation of different mechanisms. The performance of the optimized formulations was studied in vivo with 161 Large White x Landrace sows of varying parity (0–5). The sows were assigned to five groups. Group 1 (SI) received a single vulval injection of cloprostenol at 0700 h (n = 32), group 2 (SDI) received the same dose split in two parts, at 0700h and 1300h (n = 33). Group 3 (IRT) animals were administered an IR tablet at 0700h (n = 32), while group 4 (IRCRT) received both IR and CR tablets at 0700 h (n = 33). Group 5 was untreated and served as a control (n = 32). The interval to farrowing was longer (p 0.001) for controls than for treated sows, but there were no differences among cloprostenol treatments for timing of farrowing. The finding confirms the efficacy of the NVDDS for induction of farrowing in sows.
Molecular simulation driven experiment for formulation of fixed dose combination of Darunavir and Ritonavir as anti-HIV nanosuspension
Publisher: Elsevier BV
Date: 11-2019
Multifunctional Iron Bound Lactoferrin and Nanomedicinal Approaches to Enhance Its Bioactive Functions
Publisher: MDPI AG
Date: 26-05-2015
Development of PIK-75 nanosuspension formulation with enhanced delivery efficiency and cytotoxicity for targeted anti-cancer therapy
Publisher: Elsevier BV
Date: 06-2013
DOI: 10.1016/J.IJPHARM.2013.04.057
Abstract: PIK-75 is a phosphatidylinositol 3-kinase (PI3K) inhibitor that shows selectivity toward p110-α over the other PI3K class Ia isoforms p110-β and p110-δ, but it lacks solubility, stability and other kinase selectivity. The purpose of this study was to develop folate-targeted PIK-75 nanosuspension for tumor targeted delivery and to improve therapeutic efficacy in human ovarian cancer model. High pressure homogenization was used to prepare the non-targeted and targeted PIK-75 nanosuspensions which were characterized for size, zeta potential, entrapment efficiency, morphology, saturation solubility and dissolution velocity. In vitro analysis of drug uptake, cell viability and cell survival was conducted in SKOV-3 cells. Drug pharmacokinetics and pAkt expression were determined in SKOV-3 tumor bearing mice. PIK-75 nanosuspensions showed an improvement in dissolution velocity and an 11-fold increase in saturation solubility over pre-milled PIK-75. In vitro studies in SKOV-3 cells indicated a 2-fold improvement in drug uptake and 0.4-fold decrease in IC50 value of PIK-75 following treatment with targeted nanosuspension compared to non-targeted nanosuspension. The improvement in cytotoxicity was attributed to an increase in caspase 3/7 and hROS activity. In vivo studies indicated a 5-10-fold increased PIK-75 accumulation in the tumor with both the nanosuspension formulations compared to PIK-75 suspension. The targeted nanosuspension showed an enhanced downregulation of pAkt compared to non-targeted formulation system. These results illustrate the opportunity to formulate PIK-75 as a targeted nanosuspension to enhance uptake and cytotoxicity of the drug in tumor.
A validated high performance liquid chromatographic method for analysis of nicotine in pure form and from formulations
Publisher: Elsevier BV
Date: 07-2003
DOI: 10.1016/S0731-7085(03)00236-X
Abstract: A reverse phase HPLC method using C18 column has been developed for the quantitative estimation of nicotine in the bulk material and formulations (extended release and immediate release dosage forms). The method is specific to nicotine (RT approximately 4.64 min, asymmetry approximately 1.75), and can resolve analyte peak from excipient interferences. It is linear (coefficient of variation approximately 0.9993), accurate (average recovery approximately 100%), and passed all the system suitability requirements. Applicability of the method was evaluated in analysis of drug-excipient compatibility s les, commercial dosage form (such as nicotine gum) and two novel in-house formulations.
Separation and Identification of Degradation Products in Abamectin Formulation Using LC, LTQ FT-MS, H/D Exchange and NMR
Publisher: Bentham Science Publishers Ltd.
Date: 10-2012
Microbicide delivery: formulation technologies and strategies
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2008
Lipid-based nanosystem of edaravone: development, optimization, characterization and in vitro/in vivo evaluation
Publisher: Informa UK Limited
Date: 2017
Formulation and pharmacokinetics of lipid nanoparticles of a chemically sensitive nitrogen mustard derivative: Chlorambucil
Publisher: Elsevier BV
Date: 02-2009
DOI: 10.1016/J.IJPHARM.2008.09.032
Abstract: Lipid nanoparticles of the cancer drug Chlorambucil (CLB) were prepared by ultrasonication, using stearic acid as the core lipid. Four types of lipid nanoparticle formulations were studied: (i) stearic acid solid lipid nanoparticles (SLN) (ii) sterically stabilized SLN with pegylated phospholipids as stabilizer (iii) nanostructured lipid complexes with oleic acid as adjunct lipid (iv) lipid nanocomplexes with dimethyl dioctadecyl ammonium bromide (DDAB) as surface modifier (LN). Lipid nanoparticles were characterized for particle size, assay and encapsulation efficiency, particle morphology and physico-chemical stability over 90 days. All of the formulations were physically stable, with an average particle size of 147 (+/-10)nm. The drug encapsulation efficiency (DEE) of all the formulations except LN decreased significantly over time (p 0.01), indicating electrostatic charge mediated clearance, as reported earlier. In tissue and tumor distribution studies, lower AUC values of CLB were observed for LN compared to CLB solution in liver, kidneys, heart and lungs. However, higher AUC values of LN formulation as compared to CLB solution (p<0.01) in tumors suggested that the presence of DDAB on the lipid nanoparticles resulted in greater accumulation of the drug in tumors.
Inhibition of the growth and development of asexual and sexual stages of drug-sensitive and resistant strains of the human malaria parasite Plasmodium falciparum by Neem (Azadirachta indica) fractions
Publisher: Elsevier BV
Date: 05-1998
DOI: 10.1016/S0378-8741(98)00012-9
Abstract: Neem (Azadirachta indica) has been shown to possess anti-malarial activity. In this study we systematically evaluated extracts of neem seeds and purified fractions further enriched in polar or non-polar constituents for their effect on in vitro growth and development of asexual and sexual stages of the human malaria parasite Plasmodium falciparum. Use of synchronized stages of parasites suggested trophozoites/schizonts as the susceptible target stages to various neem extracts. In addition, all the maturation stages of gametocytes were also killed by various neem fractions tested. The anti-plasmodial effect of neem components was also observed on parasites previously shown to be resistant to other anti-malarial drugs, i.e. chloroquine and pyrimethamine suggesting a different mode of action. Neem seed fractions are thus active not only against the parasite stages that cause the clinical infection but also against the stages responsible for continued malaria transmission.
A Modified Approach to Predict Dissolution and Absorption of Polydisperse Powders
Publisher: Springer Science and Business Media LLC
Date: 04-06-2008
DOI: 10.1007/S11095-008-9630-3
Abstract: Particle size of a drug is an important factor that affects thermodynamic solubility and oral absorption of drug molecules. Weight fraction of different particle sizes in a polydisperse powder together with Noyes Whitney parameters (diffusion coefficient, solubility, density of the drug, boundary layer thickness and dissolution volume) can be used to predict dissolution and absorption of drug molecules. Such a simulation can be a valuable tool in setting up guidance with regards to dependence of dissolution and absorption on particle size. In this note a modified method is reported to predict dissolution of polydisperse drug powder. These use simplified equations developed from a set of differential equations described previously. The idea was to convert all the terms in one single equation which can then be solved by a Matlab program. Discrepancies not reported earlier have been discussed to get the same results as reported previously.
3D printed bilayer mucoadhesive buccal film of estradiol: impact of design on film properties, release kinetics and predicted in vivo performance
Publisher: Elsevier BV
Date: 11-2022
DOI: 10.1016/J.IJPHARM.2022.122324
Abstract: Despite being an effective therapy for menopausal symptoms, the use of oral estrogen is associated with low bioavailability and serious adverse effects of venous thromboembolism. In idualized therapy has been recommended to maximize benefits and curb the adverse effects, but much has not been done in developing formulations that offer flexibility to personalize therapy. In the present study, we employed an innovative 3D printing technology to design and develop bi-layered estradiol film with different infill patterns with an aim of improving bioavailability and facilitating personalized treatment. Hydroxypropyl cellulose (HPC-H) based formulation exhibited suitable rheological properties and was used as a feedstock to fabricate estradiol films with different infill patterns namely honeycomb, rectangular and plain. The back layer was prepared from a hydroxyethyl cellulose-based formulation. The resulting films were subsequently characterized in terms of their physicochemical, mechanical, environmental impact, and release characteristics among others. Films with a plain infill pattern exhibited significantly higher % elongation break and tensile strength. The in vitro drug release study revealed the fastest drug release profile for rectangular infill (96 % within 4 h) and the slowest drug release was observed for the plain infill pattern (∼35 % within 4 h), highlighting the effect of the infill pattern on release kinetics. Films with honeycomb infill patterns were selected for further characterization based on mechanical and in vitro release properties. No interaction between components of the formulation was observed and the absence of crystallinity in the final product was confirmed by Differential Scanning Calorimetry (DSC) and X-Ray Powder Diffraction analyses (XRD). The force of adhesiveness for the film was 0.13 ± 0.03 N. The predicted AUC 0-4 h, C
Evaluation of Transdermal Drug Permeation as Modulated by Lipoderm and Pluronic Lecithin Organogel
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.XPHS.2017.09.008
Abstract: The transdermal delivery of 2 fluorescent probes with similar molecular weight but different lipophilicity, into and through the skin from 2 commercially available transdermal bases, pluronic lecithin organogel, and Lipoderm
Synthesis and characterization of pH-sensitive inulin conjugate of isoniazid for monocyte-targeted delivery
Publisher: MDPI AG
Date: 28-10-2019
DOI: 10.3390/PHARMACEUTICS11110555
Abstract: The use of particles for monocyte-mediated delivery could be a more efficient strategy and approach to achieve intracellular targeting and delivery of antitubercular drugs to host macrophages. In this study, the potential of inulin microparticles to serve as a drug vehicle in the treatment of chronic tuberculosis using a monocytes-mediated drug targeting approach was evaluated. Isoniazid (INH) was conjugated to inulin via hydrazone linkage in order to obtain a pH-sensitive inulin-INH conjugate. The conjugate was then characterized using proton nuclear magnetic resonance (1HNMR), Fourier transform infrared spectroscopy (FTIR) as well as in vitro, cellular uptake and intracellular Mycobacterium tuberculosis (Mtb) antibacterial efficacy. The acid-labile hydrazone linkage conferred pH sensitivity to the inulin-INH conjugate with ~95, 77 and 65% of the drug released after 5 h at pH 4.5, 5.2, and 6.0 respectively. Cellular uptake studies confirm that RAW 264.7 monocytic cells efficiently internalized the inulin conjugates into endocytic compartments through endocytosis. The intracellular efficacy studies demonstrate that the inulin conjugates possess a dose-dependent targeting effect against Mtb-infected monocytes. This was through efficient internalization and cleavage of the hydrazone bond by the acidic environment of the lysosome, which subsequently released the isoniazid intracellularly to the Mtb reservoir. These results clearly suggest that inulin conjugates can serve as a pH-sensitive intracellular drug delivery system for TB treatment.
Swelling-controlled drug delivery systems
Publisher: The Royal Society of Chemistry
Date: 09-07-2018
Abstract: The increased understanding of molecular aspects associated with chronic diseases, such as cancer and the role of tumor microenvironment, has led to the identification of endogenous and exogenous stimuli that can be exploited to devise “stimuli-responsive” materials for site-specific drug delivery applications. This book provides a comprehensive account on the design, materials chemistry, and application aspects behind these novel stimuli-responsive materials. Setting the scene, the editors open with a chapter addressing the need for smart materials in delivery applications for therapy, imaging and disease diagnosis. The following chapter describes the key physical and chemical aspects of smart materials, from lipids to polymers to hybrid materials, providing the reader with a springboard to delve into the more application oriented chapters that follow. With in-depth coverage of key drug delivery systems such as pH-responsive, temperature responsive, enzyme-responsive and light responsive systems, this book provides a rigorous foundation to the field. A perfect resource for graduate students and newcomers, the closing chapter on regulatory and commercialization challenges also makes the book ideal for those wanting to take the next step towards clinical translation.
Microencapsulation of growth factors by microfluidic system
Publisher: Elsevier BV
Date: 2021
The development of 5-fluorouracil biodegradable implants: A comparative study of PCL/PLGA blends
Publisher: Elsevier BV
Date: 03-2023
Evaluation of mucoadhesive coatings of chitosan and thiolated chitosan for the colonic delivery of microencapsulated probiotic bacteria
Publisher: Informa UK Limited
Date: 03-07-2012
DOI: 10.3109/02652048.2012.700959
Abstract: Probiotic bacteria were previously encapsulated in sub-100 µm Ca(2+) alginate microcapsules for enhanced survival in human gastrointestinal tract. The aim of this study is to evaluate the altered mucoadhesive property of the probiotic delivery system by coating it with mucoadhesive chitosan or thiolated chitosan, for prolonged retention in human colon. The results confirmed that cross-linking with calcium ions reduced the mucoadhesive property of alginate hydrogel, thus questioning the intrinsic mucoadhesiveness of uncoated systems. In contrast, chitosan and thiolated chitosan were found to be adsorbed on sub-100 µm Ca(2+) alginate microcapsules, and substantially improved the mucoadhesion performance of the system. The adhesion performance was correlated to the amount of mucoadhesive coating polymer adsorbed on the surface of the system. The coated system was demonstrated on HT29-MTX colonic epithelial monolayer to deliver markedly higher amount of probiotic bacteria to the in vitro model of colonic mucosa. Additionally, the coatings were also found to exert significantly stronger mucoadhesion to colonic mucosa tissue at slight acid neutral pH with less ambient water, which conforms to the physiological environment of the colon, thus supporting prolonged retention in this region.
Biological Activity Assessment of a Novel Contraceptive Antimicrobial Agent
Publisher: Wiley
Date: 06-05-2005
Abstract: Microbicides are a new category of compounds being developed as a prophylactic approach for the prevention of transmission of sexually transmitted diseases (STDs), including the human immunodeficiency virus (HIV). These are primarily being developed as women-controlled methods, with the target of designing new compounds or formulations that can be used without the knowledge of a male partner. Microbicide screening can be initially based on their hyaluronidase-inhibiting (HI) activity, as this enzyme plays a major role in the sperm and microbe penetration into the substrate. Derivatives of hesperidin, a citrus flavonoid glycoside, have been reported in the literature for their HI effects. Hesperidin was thereby sulphonated under strictly controlled conditions and the active fraction isolated and characterized, based on its HI activity. This derivative was screened for antimicrobial and enzyme-inhibitory activities, specifically for the reproductive tract. Sulphonated hesperidin (SH) was found to completely inhibit the sperm enzymes hyaluronidase, giving an indication toward its contraceptive effects. It was also been found to inhibit various sexually transmitted pathogens, including Chlamydia trachomatis, Neisseria gonorrhoea, HIV, and Herpes Simplex virus type 2 (HSV-2). Its safety assessment was based on its noninterference in sperm motility and its penetration through the cervical mucus, and no effect on the growth of lactobacilli, the normal vaginal flora. It was also found to be nontoxic to the HIV substrate cells (MT2 cells). The study concludes that sulphonated hesperidin can be developed as a potential microbicide for a dual prophylaxis of contraception and transmission of STDs and AIDS.
Electrochemically controlled drug delivery based on intrinsically conducting polymers
Publisher: Elsevier BV
Date: 08-2010
DOI: 10.1016/J.JCONREL.2010.03.023
Abstract: This paper reviews the application of intrinsically conducting polymers (ICPs) in drug delivery. ICPs are organic polymers with electrical, magnetic and optical properties usually associated with metals, whilst retaining the advantageous mechanical properties and ease of processing usually associated with polymers. Due to the inherent properties of these unique materials, electrical stimulation can be used to alter the redox state of ICPs, which in turn can modify the release rate of drug. The controlled release of drugs from ICPs has been reported in the literature since the 1980s. Following continued development, clinical applications of ICP-based drug delivery systems (DDS) have been reported recently. The next generation of controlled release technologies could utilise the biosensing properties of ICPs combined with their drug delivering abilities to develop an intelligent drug delivery system from a single material where the release rate of drug self adjusts in response to a sensed change in local body environment. This article provides an overview of ICP synthesis and properties relevant to their use as DDS, including biodegradability and biocompatibility, followed by literature on ICP-based DDS examining different methods of drug incorporation and release. The pharmaceutical applications of these systems have also been discussed. It is concluded that ICPs hold great promise in drug delivering implants where the dose can be adjusted through application of external stimulus, thus optimising benefit to side effect ratio while simultaneously ensuring patient adherence.
<p>Perindopril in Breast Milk and Determination of Breastfed Infant Exposure: A Prospective Observational Study</p>
Publisher: Informa UK Limited
Date: 03-2020
DOI: 10.2147/DDDT.S239704
Development of a Controlled Release System for Risperidone Using Polypyrrole: Mechanistic Studies
Publisher: Wiley
Date: 02-2010
The application of flow cytometry to the characterisation of a probiotic strain Lactobacillus reuteri DPC16 and the evaluation of sugar preservatives for its lyophilization
Publisher: Elsevier BV
Date: 11-2011
Pharmacokinetics and pharmacodynamics of chlorambucil delivered in long-circulating nanoemulsion
Publisher: Informa UK Limited
Date: 12-01-2010
DOI: 10.3109/10611860903244199
Abstract: Chlorambucil was incorporated into a nanoemulsion modified with poly(ethylene glycol) to improve its pharmacokinetics and tissue distribution, and thus enhance its therapeutic efficacy. A long-circulating nanoemulsion (LNE) was prepared using soybean oil, egg lecithin, cholesterol and PEG(2000)DSPE. The LNE had an oil droplet size <200 nm with a surface charge of -32.2 to -35.6 mV. Approximately, 97% of the chlorambucil was encapsulated in the LNE. Intravenous (i.v.) administration of the chlorambucil LNE to C57 B/6 mice showed improved pharmacokinetic parameters with 1.4-fold higher area under the plasma concentration-time curve (AUC) and 1.3-fold longer half-life compared to a non-PEG-modified nanoemulsion, and 2.7-fold higher AUC and 7.6-fold longer half-life compared to chlorambucil solution. Tissue distribution studies after i.v. administration with LNE showed a considerable decrease in drug uptake in the reticulo-endothelial system containing organs compared to non-PEG-modified nanoemulsion. Additionally, the chlorambucil delivered in LNE significantly enhanced therapeutic efficacy in the subcutaneous colon-38 adenocarcinoma tumor mouse model with no apparent increase in toxicity. This study suggests that LNE could produce remarkably improved pharmacokinetic profile and therapeutic efficacy of chlorambucil compared to non-PEG-modified nanoemulsion and solution.
Development and preclinical evaluation of microneedle-assisted resveratrol loaded nanostructured lipid carriers for localized delivery to breast cancer therapy
Publisher: Elsevier BV
Date: 09-2021
Engineering of a dual-modal phototherapeutic nanoplatform for single NIR laser-triggered tumor therapy
Publisher: Elsevier BV
Date: 07-2021
Effect of wet milling process on the solid state of indomethacin and simvastatin
Publisher: Elsevier BV
Date: 10-2009
DOI: 10.1016/J.IJPHARM.2009.06.029
Abstract: The aim of this study was to investigate the effect of wet milling on the solid state of indomethacin (IMC) and simvastatin (SIM). Wet milling was performed using high pressure homogenization (HPH). Polyvinylpyrrolidone-K25 (PVP) and poloxamer 407 (P407) were used as suspension stabilizers. S les were characterized before and after wet milling using particle size analyzer, scanning electron microscopy (SEM), infrared (IR) spectroscopy and modulated temperature differential scanning calorimetry (MTDSC) techniques. After wet milling of IMC, physical appearance and IR spectra indicated surface amorphization however, the solid state of SIM remained unaffected. MTDSC could not detect surface amorphization in IMC, suggesting that if present, it was only at very low levels. These results are in contradiction to the previous reports where dry milling of IMC and SIM resulted in amorphization of crystalline particles. Moreover, cryogrinding of IMC in the absence of water resulted in an amorphous form while presence of water using the same cryogrinding conditions resulted in a solid state similar to that obtained after wet milling. These results signify the role of water in inhibiting the amorphization during wet milling of crystalline drugs.
Separation and identification of degradation products in eprinomectin formulation using LC, LTQ FT-MS, H/D exchange, and NMR
Publisher: Elsevier BV
Date: 04-2012
DOI: 10.1016/J.JPBA.2011.12.030
Abstract: The aim of this study was to evaluate the suitability of the compendial active pharmaceutical ingredient (API) method for the analysis of finished products and characterization of degradation products in eprinomectin (EPM) s les. Heat stressed s le tests revealed a limitation of the API method in distinguishing an impurity merging with the principal analyte peak. A new selective, specific and sensitive method was therefore developed for the determination of EPM in formulations that separates its degradation products currently undetectable with the official method. The determination was carried out by reversed-phase HPLC using an isocratic solvent elution. The method was validated and found to be precise, accurate and specific the detector response was linear over 50-150 μg/ml (EPM) and 0.1-3 μg/ml (degradation product) range of concentrations. Two major degradation products detected with the new method were isolated from s le matrices and characterized using LC-PDA, high resolution FT-ICR MS, NMR and hydrogen/deuterium exchange (HX-MS) studies. FTMS analysis showed accurate mass of molecular ion peaks for EPM and its two degradation products at m/z 914.52505 (mass error ≤ 1 ppm) with almost identical fragmentation patterns. Given the isomeric nature of the compounds, all three were further evaluated by ¹H, ¹³C, 1D NOESY and 2D (COSY) NMR experiments. The interpretation of experimental data positively identified Unknown 1 as the 2-epimer of EPM and Unknown 2 as the structural isomer Δ2,3-EPM containing a conjugated enoate. The new HPLC method and identification exercise is useful for analysis of EPM and its degradation products.
Synergistic spermicidal activity of neem seed extract, reetha saponins and quinine hydrochloride
Publisher: Elsevier BV
Date: 08-1994
DOI: 10.1016/0010-7824(94)90054-X
Abstract: In order to identify potent spermicidal agents which are free from the side effects of currently available agents, spermicidal activity of purified neem seeds extract (Praneem), reetha saponins and quinine hydrochloride was studied in idually and in combination. Sander-Cramer test was used to assess the activity on human sperm. Under the test conditions, minimum effective spermicidal concentrations for Praneem, reetha saponins and quinine hydrochloride were 25%, 0.05% and 0.346%, respectively. At these concentrations, 100% of the sperm were immobilised within 20 seconds. A positive synergistic effect in the spermicidal activity of these components, if used in combination, was observed which implies the use of reduced concentrations of each to bring about the desired action. The selected combination formulated into a suitable dosage form is likely to offer dual benefit of a potent contraceptive and an antimicrobial preparation.
Power outages and refrigerated medicines: The need for better guidelines, awareness and planning
Publisher: Hindawi Limited
Date: 13-06-2018
DOI: 10.1111/JCPT.12716
Abstract: Vaccines and other pharmaceuticals are essential medical supplies that require continuous storage at specific temperatures to maintain viability. Power outages can lead to a break in the cold chain, resulting in the degradation of essential medicines. After a power outage, the stability of vaccines and other medicines can be difficult to ascertain. Many public health guidelines therefore recommend discarding potentially compromised pharmaceuticals unless the cold chain can be guaranteed-a costly endeavour. There are government guidelines aimed at minimizing exposure to high temperatures in the event of a power outage however, the usefulness of these guidelines is uncertain. The actual cost of vaccine and pharmaceutical loss due to a break in the cold chain is poorly studied and requires further research. Additional recommendations regarding the stability of specific medicines would also be a valuable resource.
Development of Novel Sustained Release Bioadhesive Vaginal Tablets of Povidone Iodine
Publisher: Informa UK Limited
Date: 2007
DOI: 10.1080/03639040701385782
Abstract: Iodine has long been used as an antiseptic for the prevention and treatment of vaginal infections. The present study was aimed at the development of rapidly disintegrating, bioadhesive and sustained release vaginal tablets of an iodophore, polyvinylpyrrolidone (povidone iodine), their evaluation and comparison with the marketed formulations. The formulation development included drug-excipient compatibility studies, optimization of performance parameters like disintegration time, bioadhesion and drug release profile and comparison of physical properties and performance parameters with the marketed formulation. The developed formulation provided a sustained release of polymer complexed iodine (up to 8 hrs), rapid disintegration (< 1 min.), desired bioadhesive properties and retention for a prolonged time.
Mesoporous silica nanoparticles for drug combination delivery in cancer therapy: background, current insights, and future perspectives
Publisher: Elsevier
Date: 2021
Development and Validation of a HPLC Method for Simultaneous Determination of Dapivirine and DS003 in Combination Microbicide Tablet
Publisher: Bentham Science Publishers Ltd.
Date: 02-2011
In Vitro and In Vivo Assessment of Docetaxel Formulation Developed for Esophageal Stents
Publisher: Springer Science and Business Media LLC
Date: 19-02-2016
DOI: 10.1208/S12249-016-0501-7
Abstract: Esophageal cancer (EC) mostly affects the elderly population and is frequently diagnosed at an advanced stage. Self-expanding metal stents (SEMS) are the most popular mode of palliation, but they are associated with reocclusion caused by tumor growth. To overcome this problem, docetaxel (DTX)-loaded polyurethane formulations were prepared for stent application. The films were evaluated against the cancer cell lines, OE-19 and OE-21, and normal esophageal cell line Het-1A. The DTX and the formulations were evaluated in vitro for the cytotoxicity and in vivo in nude mice. It was found that DTX and the formulations have a weak activity against the EC cell lines and an even weaker activity against Het-1A cell line. Preliminary in vivo studies showed skin toxicity in nude mice necessitating modification of the formulation. Reevaluation in a mouse xenograft model resulted in toxicity at high dose formulations while the low dose formulation exhibited modest advantage over commercial IV formulation however, there was no significant difference between the commercial IV and blank formulation. DTX combination with an anti-cancer agent having complementary mode of action and non-overlapping toxicity could yield better outcome in future.
Conducting polymers with defined micro- or nanostructures for drug delivery
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.BIOMATERIALS.2016.09.021
Abstract: Conducting polymers (CPs) are redox active materials with tunable electronic and physical properties. The charge of the CP backbone can be manipulated through redox processes, with accompanied movement of ions into and out of the polymer to maintain electrostatic neutrality. CPs with defined micro- or nanostructures have greatly enhanced surface areas, compared to conventionally prepared CPs. The resulting high surface area interface between polymer and liquid media facilities ion exchange and can lead to larger and more rapid responses to redox cycling. CP systems are maturing as platforms for electrically tunable drug delivery. CPs with defined micro- or nanostructures offer the ability to increase the amount of drug that can be delivered whilst enabling systems to be finely tuned to control the extent and rate of drug release. In this review, fabrication approaches to achieve CPs with micro- or nanostructure are outlined followed by a detailed review and discussion of recent advances in the application of the materials for drug delivery.
Osmotically Controlled Oral Drug Delivery*
Publisher: Informa UK Limited
Date: 2000
Abstract: It is advantageous to deliver some drugs with short half-life, and which are to be given frequently for chronic ailments, in the form of controlled-release (CR) formulations. The orally administered drugs, in the form of conventional matrix or reservoir type formulations, pose problems of bioavailability fluctuations due to gastric pH variations. Moreover, the release of drug(s) from these systems is affected by the hydrodynamic conditions of the body. Osmotically controlled drug delivery systems utilize the principles of osmotic pressure for the controlled delivery of active agent(s). The release rate of drug(s) from these systems is independent of the physiological factors of the gastrointestinal (GI) tract to a large extent. In the present review, theory underlying the delivery of drugs from osmotic systems is presented. Different types of oral osmotic systems, their advantages over conventional matrix and reservoir types of systems, and their applications are also discussed. Finally, some of the limitations, adverse effects, and patent and market status of these systems are reviewed. These systems form a major segment of drug delivery products. Because of their advantages and strong market potential, it appears that the future of osmotic systems in rate-controlled oral drug delivery is promising.
Extemporaneous compounding in veterinary practice: A New Zealand perspective
Publisher: Informa UK Limited
Date: 11-2013
DOI: 10.1080/00480169.2013.773853
Abstract: The aims of this study were to explore the extent of extemporaneous compounding in veterinary centres throughout New Zealand and to determine whether pharmacists could collaborate with veterinarians to improve this service in New Zealand. Questionnaires were sent to 200 randomly selected veterinarians in New Zealand. Semi-structured interviews were also conducted with selected participants from four animal facilities (zoos, research facilities and animal shelters) and two compounding pharmacies. Of the 200 veterinarian questionnaire recipients, 99 responded. Ten replies were withdrawn from the study giving a response rate of 44.5%. Of these 89, 33 (37%) compounded in their practice. Of the 33 compounding professionals, 3 (9%) compounded daily for animals under their care 11 (34%) weekly, 18 (54%) monthly and 1 (3%) compounded yearly. Compounding was done by 29/33 (88%) veterinarians, 16/33 (48%) veterinary nurses or 6/33 (18%) others. It was carried out due to the unavailability of commercial products, or the need for dose adjustment to ease administration or improve compliance. The animals most commonly requiring veterinary compounding were dogs (21/33 64%), cats (19/33 58%) or cattle (15/33 46%). Products which were commonly compounded included cyclosporin eye drops, methimazole gels and potassium bromide solutions. Issues commonly faced when compounding included unavailability of dosage forms (18/33 55%) or appropriate ingredients (14/33 42%), stability (12/33 36%), time constraints (10/33 30%) or unavailability of equipment (9/33 27%). Reasons given for not compounding included medicines being commercially available (38/56 68%), pharmacy compounding for those particular practices (24/56 43%), lack of training (21/56 38%), ingredients (16/56 29%) or equipment (15/56 11%). All participants who worked with a pharmacist (11/33 33%) described this relationship as beneficial and indicated they would continue to do so in the future. Veterinary extemporaneous compounding exists in New Zealand. As pharmacists have extensive knowledge in formulating medications and compounding they could be of greater value to veterinarians and their patients. Educating both professions on the opportunities available to them from this collaboration could be an important step forward. This study provides new information regarding extemporaneous compounding for veterinary patients in New Zealand.
Hydrogels: from controlled release to pH-responsive drug delivery
Publisher: Elsevier BV
Date: 05-2002
DOI: 10.1016/S1359-6446(02)02255-9
Abstract: Hydrogels are one of the upcoming classes of polymer-based controlled-release drug delivery systems. Besides exhibiting swelling-controlled drug release, hydrogels also show stimuli-responsive changes in their structural network and hence, the drug release. Because of large variations in physiological pH at various body sites in normal as well as pathological conditions, pH-responsive polymeric networks have been extensively studied. This review highlights the use of hydrogels (a class of polymeric systems) in controlled drug delivery, and their application in stimuli-responsive, especially pH-responsive, drug release.
Formulation aspects in the development of osmotically controlled oral drug delivery systems
Publisher: Elsevier BV
Date: 19-02-2002
DOI: 10.1016/S0168-3659(01)00550-8
Abstract: Osmotically controlled oral drug delivery systems utilize osmotic pressure for controlled delivery of active agent(s). Drug delivery from these systems, to a large extent, is independent of the physiological factors of the gastrointestinal tract and these systems can be utilized for systemic as well as targeted delivery of drugs. The release of drug(s) from osmotic systems is governed by various formulation factors such as solubility and osmotic pressure of the core component(s), size of the delivery orifice, and nature of the rate-controlling membrane. By optimizing formulation and processing factors, it is possible to develop osmotic systems to deliver drugs of erse nature at a pre-programmed rate. In the present review, different types of oral osmotic systems, various aspects governing drug release from these systems, and critical formulation factors are discussed.
Bioadhesive microspheres as a controlled drug delivery system
Publisher: Elsevier BV
Date: 04-2003
DOI: 10.1016/S0378-5173(03)00087-5
Abstract: The concept of controlled drug delivery has been traditionally used to obtain specific release rates or spatial targeting of active ingredients. The phenomenon of bioadhesion, introduced by Park and Robinson [Park, K., Robinson, J.R., 1984. Bioadhesive polymers as platforms for oral controlled drug delivery: method to study bioadhesion. Int. J. Pharm. 198, 107-127], has been studied extensively in the last decade and applied to improve the performance of these drug delivery systems. Recent advances in polymer science and drug carrier technologies have promulgated the development of novel drug carriers such as bioadhesive microspheres that have boosted the use of "bioadhesion" in drug delivery. This article presents the spectrum of potential applications of bioadhesive microspheres in controlled drug delivery ranging from the small molecules, to peptides, and to the macromolecular drugs such as proteins, oligonucleotides and even DNA. The development of mucus or cell-specific bioadhesive polymers and the concepts of cytoadhesion and bioinvasion provide unprecedented opportunities for targeting drugs to specific cells or intracellular compartments. Developments in the techniques for in vitro and in vivo evaluation of bioadhesive microspheres have also been discussed.
The effects of novel formulations of edaravone and curcumin in the mouse intrastriatal lipopolysaccharide model of Parkinson's disease
Publisher: IMR Press
Date: 07-05-2022
Abstract: The major hallmark of Parkinson's disease (PD) is the degeneration of dopaminergic neurons in the substantia nigra (SN), which is responsible for the core motor symptoms of PD. Currently, there is no cure for PD, and its prevalence is increasing, prompting the search for novel neuroprotective treatments. Neuroinflammation is a core pathological process in PD, evident by increased inflammatory biomarkers in the SN and cerebrospinal fluid. Interestingly, epidemiological studies have reported a reduced risk of PD in users of non-steroidal anti-inflammatory drugs compared to non-users, suggesting the neuroprotective potential of anti-inflammatory drugs. Therefore, this study aimed to: (1) test the efficacy of novel oral formulations of edaravone (EDR) and curcumin (CUR) (which possess anti-inflammatory and anti-oxidative properties) to alleviate motor and non-motor symptoms, and associated pathology in the intrastriatal lipopolysaccharide (LPS) model of PD (2) investigate the expression of proteins linked to familial PD and markers of autophagy in the intrastriatal LPS model treated with EDR and CUR. Fifty-two C57BL/6 mice were ided into 4 groups, namely (1) control + vehicle (2) LPS + vehicle (3) LPS + EDR (made in vehicle) and (4) LPS + CUR (made in vehicle). 10 μg of LPS was administered stereotaxically into the right striatum, and EDR and CUR treatments were initiated 2-weeks after the LPS injections. Behavioural tests were carried out at 4- and 8-weeks after LPS injection followed by tissue collection at 8-weeks. Intrastriatal administration of LPS induced motor deficits and anxiety-like behaviours at 4- and 8-weeks, which were accompanied by astroglial activation, increased protein expression of α-synuclein, heat shock cognate protein of 70 kDa (HSC-70) and Rab-10, and reduced levels of tyrosine hydroxylase (TH) protein in the striatum. Additionally, LPS induced astroglial activation in the olfactory bulb, along with changes in the protein expression of HSC-70. The changes associated with EDR and CUR in the striatum and olfactory bulb were not statistically significant compared to the LPS group. Intrastriatal administration of LPS induced pathological changes of PD such as motor deficits, reduced expression of TH protein and increased α-synuclein protein, as well as some alterations in proteins linked to familial PD and autophagy in the olfactory bulb and striatum, without pronounced therapeutic effects of EDR and CUR. Our results may suggest that EDR and CUR lack therapeutic effects when administered after the disease process was already initiated. Thus, our treatment regimen or the physicochemical properties of EDR and CUR could be further refined to elevate the therapeutic effects of these formulations.
Non-vascular drug eluting stents as localized controlled drug delivery platform: Preclinical and clinical experience
Publisher: Elsevier BV
Date: 11-2013
DOI: 10.1016/J.JCONREL.2013.08.010
Abstract: Stents occupy an important place in the medical field for their widespread application. They have been used in vascular as well as in non-vascular organs for various reasons. Among vascular stents, development of coronary drug eluting stents (DESs) has completely revolutionised the percutaneous coronary intervention. Similarly, attempts have been made to make use of this modality in non-vascular organs. This paper focuses on the preclinical and clinical experience with drug-eluting non-vascular stents with emphasis on drug delivery systems and regulatory requirements for their development.
Studies on the contraceptive efficacy of Praneem polyherbal cream
Publisher: Elsevier BV
Date: 12-1993
DOI: 10.1016/0010-7824(93)90120-V
Abstract: Praneem polyherbal cream, a spermicidal formulation, has been developed at the National Institute of Immunology, which makes use of Praneem, a purified extract from the dried seeds of an ancient Indian plant Azadirachta indica (Neem), extract from the pericarp of fruits of Sapindus species and quinine hydrochloride. These ingredients have a synergistic spermicidal activity and an optimised formula was derived. The components were made into a water-soluble cream base prepared by using pharmaceutically acceptable base and stabilised by addition of IP grade antioxidant and preservatives. The cream is devoid of irritation and sensitization potential, as seen with standard Draize test on normal and abraded skin of rabbits and by 21-day cumulative skin sensitivity in human volunteers. The formulation was found to be safe under subacute toxicity studies in monkeys. The formulation has shown high contraceptive efficacy in rabbits and in monkeys after intravaginal application. The shelf-life of the cream at room temperature is estimated to be 18 months by accelerated stability studies.
Targeting prostate cancer cells with genetically engineered polypeptide-based micelles displaying gastrin-releasing peptide
Publisher: Elsevier BV
Date: 11-2016
DOI: 10.1016/J.IJPHARM.2016.09.039
Abstract: In recent years G protein-coupled receptors (GPCRs) have emerged as crucial tumorigenic factors that drive aberrant cancer growth, metastasis and angiogenesis. Consequently, a number of GPCRs are strongly expressed in cancer derived cell lines and tissue s les. Therefore a rational anti-cancer strategy is the design of nano-medicines that specifically target GPCRs to bind and internalise cytotoxic drugs into cancer cells. Herein, we report the genetic engineering of a self-assembling nanoparticle based on elastin-like polypeptide (ELP), which has been fused with gastrin releasing peptide (GRP). These nanoparticles increased intracellular calcium concentrations when added to GRP receptor positive PC-3 prostate cancer cells, demonstrating specific receptor activation. Moreover, GRP-displaying fluorescent labelled nanoparticles showed specific cell-surface interaction with PC-3 prostate cancer cells and increased endocytic uptake. These nanoparticles therefore provide a targeted molecular carrier system for evaluating the delivery of cytotoxic drugs into cancer cells.
In Vitro Wound Healing Properties of Novel Acidic Treatment Regimen in Enhancing Metabolic Activity and Migration of Skin Cells
Publisher: MDPI AG
Date: 28-06-2022
DOI: 10.3390/IJMS23137188
Abstract: Strategies that alter the pH of wounds to improve healing outcomes are an emerging area of interest. Currently, there is limited understanding of the effect of hydrogen (H+) on the functionality of skin cells during proliferation and migration, highlighting the need for research to determine the effect of pH during wound healing. This study aimed to determine the effect of acidification on the metabolic activity and migration of human immortalized keratinocytes (HaCaT) and human foreskin fibroblasts (HFF). In vitro models were used with phosphoric and citric acid buffers at a pH range between 3 and 7. Our results showed that cells were more viable in buffers with low rather than high ionic strength. A time-dependent effect of the acidification treatment was also observed with cell metabolic activity varying with treatment duration and frequency. Our results showed that a 24 h treatment and subsequent resting phase significantly improved cell proliferation and migration. This in vitro study is the first to establish a correlation between the role of acidic pH, molarity and treatment regimen in cellular activity. Our data demonstrated a positive effect of acidic pH on cell metabolic activity and migration rate, suggesting a clinical potential in indications such as wound healing.
The effect of immobilization of probiotic Lactobacillus reuteri DPC16 in sub-100 μm microcapsule on food-borne pathogens
Publisher: Springer Science and Business Media LLC
Date: 30-03-2012
DOI: 10.1007/S11274-012-1046-X
Abstract: The aim of this study was to evaluate whether immobilizing a probiotic strain Lactobacillus reuteri DPC16 in chitosan-coated alginate microcapsules affected their inhibitory performance against food-borne pathogens. The probiotic strain was encapsulated in sub-100 μm alginate microspheres which were further coated with chitosan. This type of probiotic microcapsules was investigated in a co-culture model for its effect against two food-borne pathogenic bacteria. The results confirmed the comparable inhibitory performances between the planktonic and the microencapsulated DPC16 in terms of the medium acidification and the reuterin production in the presence of sufficient nutrients. However, if an infertile condition was present, in which energy source was limited, the planktonic DPC16 tended to instantly accumulate a higher concentration of reuterin but at the cost of substantial viability loss, whereas immobilization in the chitosan-coated alginate microcapsules extended the survival of DPC16, albeit with a significantly lower reuterin production. In conclusion, no attenuated antimicrobial effect was observed for the immobilized DPC16 in the co-culture model. Microencapsulation rendered an enhanced protection on the embedded probiotics, but it may also induce an altered availability of substrates to those microorganisms.
Formulation of Chitosan Stabilized Silver Nanoparticle-Containing Wound Healing Film: In Vitro and In Vivo Characterization
Publisher: Elsevier BV
Date: 07-2020
Development and application of a chromatographic method for simultaneous quantification of 5-fluorouracil and imiquimod in drug-in-adhesive topical patches
Publisher: Elsevier BV
Date: 06-2022
Influence of Polymer Composition on the Controlled Release of Docetaxel: A Comparison of Non-Degradable Polymer Films for Oesophageal Drug-Eluting Stents
Publisher: MDPI AG
Date: 11-05-2020
DOI: 10.3390/PHARMACEUTICS12050444
Abstract: Following the huge clinical success of drug-eluting vascular stents, there is a significant interest in the development of drug-eluting stents for other applications, such as the treatment of gastrointestinal (GI) cancers. Central to this process is understanding how particular drugs are released from stent coatings, which to a large extent is controlled by drug-polymer interactions. Therefore, in this study we investigated the release of docetaxel (DTX) from a selection of non-degradable polymer films. DTX-polymer films were prepared at various loadings (1, 5 and 10% w/w) using three commercially available polymers including poly(dimethylsiloxane) (PSi), poly (ethylene-co-vinyl acetate) (PEVA) and Chronosil polyurethane (PU). The formulations were characterised using different techniques such as photoacoustic Fourier-transform infrared (PA-FTIR) spectrophotometry, X-ray diffraction (XRD) and differential scanning calorimetry (DSC). The effect of DTX on the mechanical properties of the films, in-vitro release, and degradation tests were also assessed. For all polymers and DTX loadings, the drug was found to disperse homogenously without crystallisation within the polymer matrix. While no specific interactions were observed between DTX and PSi or PEVA, hydrogen-bonding appeared to be present between DTX and PU, which resulted in a concentration-dependent decrease in the Young’s moduli of the films due to disruption of inter-polymeric molecular interactions. In addition, the DTX-PU interactions were found to modulate drug release, providing near-linear release over 30 days, which was accompanied by a significant reduction in degradation products. The results indicate that DTX-loaded PU films are excellent candidates for drug-eluting stents for the treatment of oesophageal cancer.
Stability Assessment of Extemporaneous Formulation of Amoxicillin for Parenteral Antimicrobial Therapy
Publisher: Bentham Science Publishers Ltd.
Date: 10-2012
Development and evaluation of a topical anti-inflammatory preparation containing Dodonaea polyandra extract
Publisher: Frontiers Media SA
Date: 24-10-2015
DOI: 10.18433/J38P57
Abstract: Purpose: We have previously reported that the Australian Northern Kaanju (Kuuku I’yu) medicinal plant Dodonaea polyandra has anti-inflammatory activity. This is attributed largely to the presence of clerodane diterpenoids contained within the leaf resin. We envisaged developing a topical preparation to treat indications relating to skin inflammation. However, it was unknown whether the resin could be incorporated into a suitable dosage form while retaining the therapeutic value demonstrated in previous work. Therefore, the following study was undertaken to assess parameters of safety and efficacy for a prototype formulation containing the leaf resin extracted from D. polyandra. Methods: Using the assessment criteria of optimum appearance, tactile feeling, spreadability and odour, 78 different formulations were developed. Formulation stability was assessed using a centrifugal test with preparations displaying phase separation further modified or re-formulated. A prototype formulation containing 5% w/w plant resin was selected and subjected to in vitro release studies. This was quantified through HPLC analysis using two major bioactive diterpenoids as reference. The prototype formulation was tested for efficacy in a TPA-induced acute murine skin inflammation model as well as a 3D human skin model for irritancy/toxicity (Epiderm™). Results: The prototype resin cream was a chartreuse-coloured homogenous semisolid preparation that was readily spreadable upon contact with skin with no sensation of tackiness, residual greasiness, or irritation. The optimized cream showed no phase separation after 30 min centrifugation at 825 g. In the TPA-induced inflammation model, the resin formulation significantly reduced ear thickness and interleukin-1 beta levels in mouse ear tissue. The 5% w/w resin cream formulation showed no irritancy in a 3D human skin model. Conclusions: Our results demonstrate that bioactive resin from D. polyandra can be formulated into a stable and non-irritant semi-solid dosage form and reduce parameters of acute skin inflammation in vivo. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.
Ultrasmall AgNP-impregnated biocompatible hydrogel with highly effective biofilm elimination properties
Publisher: American Chemical Society (ACS)
Date: 25-08-2020
Physicochemical properties of otic products for Canine Otitis Externa: comparative analysis of marketed products
Publisher: Springer Science and Business Media LLC
Date: 09-02-2023
DOI: 10.1186/S12917-023-03596-2
Abstract: Otitis externa is a commonly diagnosed dermatological disorder in canines. The pathogens primarily involved in canine otitis externa (COE) include Staphylococcus pseudintermedius, Pseudomonas aeruginosa, Proteus mirabilis, and Malassezia pachydermatis . As COE tends to be superficial, medications delivered topically are often effective and practical in managing the condition. As such, there is a wide variety of approved topical products currently available in the market. The efficacy of topical dosage forms can be dependent on various factors such as the pharmacology of active constituents and the physicochemical properties of the formulation, including pH, viscosity, spreadability, and bio-adhesion. Currently, there is a lack of published literature available on the optimal properties of topical COE products. In this study, we compared the physicochemical properties of nine commercially available otic veterinarian products in Australia used clinically to manage COE. Based on our comparative analysis, the pH (6.26 ± 0.04) of an aqueous-based product was similar to a healthy dog’s external auditory canal. Products containing polymers exhibited higher viscosity and bio-adhesion. Spreadability was inversely related to viscosity and Osurnia ® a product with high viscosity demonstrated the lowest spreadability. Aqueous-based otic products showed better syringebility whereas oil-based systems required higher force to expel the products. Variability in droplet size was noted. Derm Otic, Baytril Otic, and Aurizon Ear Drops had the lower standard deviation which indicates they would give a more consistent dose. Findings from this work provide considerations for industry researchers or formulation scientists working in the area of otic dosage formulations.
Transpapillary iontophoretic delivery of resveratrol loaded transfersomes for localized delivery to breast cancer
Publisher: Elsevier BV
Date: 09-2022
DOI: 10.1016/J.BIOADV.2022.213085
Abstract: Localized drug delivery to the breast tissues is an area of interest as a potential route to ensure site-specific drug delivery. Transpapillary delivery via the mammary papilla has advantages as most breast tumors arise from the milk ducts. The present study explored the plausibility of transpapillary delivery of a phytochemical, resveratrol (RVT), for breast cancer treatment. RVT was encapsulated within the transfersomes (RVT-TRF) to enable a sustained release of the drug using the biomaterial soya phosphatidylcholine (SPC). Iontophoresis was applied to further accelerate the penetration of the RVT-TRF across the mammary papilla to the breast tissue. The RVT-TRF development was optimized by the Design of Experiments (DoE) approach. The in vitro transpapillary iontophoresis study on porcine mammary papilla showed an enhanced penetration of RVT-TRF when compared to passive diffusion. The transpapillary delivery was further confirmed from the in vitro fluorescent microscopy study using FITC conjugated RVT-TRF. The optimized RVT-TRF delivered via transpapillary route showed a higher C
Harnessing the Synergistic Potential of 3D Printed Buccal Films and Nanostructured Lipid Carriers (NLCs) For Personalised Cannabidiol Delivery
Publisher: Research Square Platform LLC
Date: 31-05-2023
DOI: 10.21203/RS.3.RS-2945517/V1
Abstract: Introduction : Cannabidio(CBD) has been recognized for its numerous therapeutic benefits, such as neuroprotection, anti-inflammatory effects, and cardioprotection. However, CBD has some limitations, including unpredictable pharmacokinetics and low oral bioavailability. To overcome the challenges associated with CBD delivery, we employed Design of Experiments (DoE), lipid carriers, and 3D printing techniques to optimize and develop buccal film loaded with CBD-NLCs. Methods : Three-factor Box-Behnken Design was carried out to optimise the NLCs and analyse the effect of independent factors on dependent factors. The emulsification-ultrasonication technique was used to prepare the NLCs. A pressure-assisted micro-syringe printing technique was used to produce the films. The produced films were studied for physicochemical, and mechanical properties, release profiles, and predicted in vivo performance. Results : The observed particle size of the NLCs ranged from 12.17 to 84.91nm whereas the PDI varied from 0.099 to 0.298. Lipid and sonication time positively affected the particle size whereas the surfactant concentration was inversely related. CBD was incorporated into the optimal formulation and the observed particle size, PDI, and zeta potential for the CBD-NLCs were 94.2 ±0.47nm, 0.11± 0.01 and−11.8 ± 0.52 mV. Hydroxyethyl cellulose (HEC)-based gel containing the CBD-NLCs was prepared and used as a feed for 3D printing. The CBD-NLCs film demonstrated a two-phase in vitro release profile, wherein an initial burst release of 47% occurred within the first 2h. The predicted AUC 0–10 h, C max , and T max were 201.5µg·h/L, 0.74 µg/L, and 1.28 h for a film with 0.4 mg of CBD, respectively. Conclusion: The finding demonstrates that a buccal film of CBD-NLCs can be fabricated using 3D printing.
Trends in nanotechnology-based delivery systems for dermal targeting of drugs: an enticing approach to offset psoriasis
Publisher: Informa UK Limited
Date: 14-05-2020
Synthesis and Characterization of Thermo-Sensitive Nanoparticles for Drug Delivery Applications
Publisher: American Scientific Publishers
Date: 12-2008
DOI: 10.1166/JBN.2008.014
Abstract: The aim of this research project was to develop new temperature sensitive nanoparticles that have a lower critical solution temperature (LCST) that is above body temperature and can be incorporated with various molecules at the surface. The poly( N -isopropylacrylamide-co-acrylamide-co-allylamine) (NIPA-AAm-AH) nanoparticles were synthesized through a free radical polymerization method. NIPA was polymerized with AAm and AH to increase the LCST and to provide amine groups for functionalization, respectively. Using transmission electron microscopy (TEM) and laser scattering technology, the sizes of these nanoparticles were found to be inversely proportional to the surfactant concentrations. In addition, the LCST of the 100-nm NIPA-AAm-AH nanoparticles was approximately 40 °C measured by a spectrophotometer. The chemical composition of the NIPA-AAm-AH nanoparticles determined with Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) also confirmed the presence of functional groups of each monomer. Moreover the nanoparticles were successfully conjugated to bovine anti-rabbit IgG-Texas Red as a model for future bioconjugation. Furthermore, nanoparticles did not show significant cytotoxicity activity against human fibroblast cells. Finally, doxorubicin (DOX) was used in order to investigate the drug release profiles of the NIPA-AAm-AH nanoparticles at different temperatures. The results indicated that DOX was released more at 41 °C compared to that of 37 °C and 4 °C, which is evidence for temperature sensitivity of the nanoparticles. Future work will investigate the pharmacological and targeted capabilities of the synthesized nanoparticles conjugated to antibodies for possible application in controlled and targeted drug delivery.
Pharmaceutical Development of 5-Fluorouracil-Eluting Stents for the Potential Treatment of Gastrointestinal Cancers and Related Obstructions
Publisher: Informa UK Limited
Date: 04-2021
DOI: 10.2147/DDDT.S299401
Pancreatic Cancer: Challenges and Opportunities in Locoregional Therapies
Publisher: MDPI AG
Date: 31-08-2022
Abstract: Pancreatic cancer (PC) remains the seventh leading cause of cancer-related deaths worldwide and the third in the United States, making it one of the most lethal solid malignancies. Unfortunately, the symptoms of this disease are not very apparent despite an increasing incidence rate. Therefore, at the time of diagnosis, 45% of patients have already developed metastatic tumours. Due to the aggressive nature of the pancreatic tumours, local interventions are required in addition to first-line treatments. Locoregional interventions affect a specific area of the pancreas to minimize local tumour recurrence and reduce the side effects on surrounding healthy tissues. However, compared to the number of new studies on systemic therapy, very little research has been conducted on localised interventions for PC. To address this unbalanced focus and to shed light on the tremendous potentials of locoregional therapies, this work will provide a detailed discussion of various localised treatment strategies. Most importantly, to the best of our knowledge, the aspect of localised drug delivery systems used in PC was unprecedentedly discussed in this work. This review is meant for researchers and clinicians considering utilizing local therapy for the effective treatment of PC, providing a thorough guide on recent advancements in research and clinical trials toward locoregional interventions, together with the authors’ insight into their potential improvements.
A bibliometric review of pharmacy education literature in the context of low- to middle-income countries
Publisher: Elsevier BV
Date: 05-2013
Clinical trials in New Zealand: Progress, people, and policies
Publisher: Wiley
Date: 30-12-2010
DOI: 10.1002/DDR.20437
Crystal modifications and dissolution rate of piroxicam
Publisher: Walter de Gruyter GmbH
Date: 12-2011
DOI: 10.2478/V10007-011-0037-Z
Abstract: Piroxicam is a nonsteroidal anti-inflammatory drug with low aqueous solubility which exhibits polymorphism. The present study was carried out to develop polymorphs of piroxicam with enhanced solubility and dissolution rate by the crystal modification technique using different solvent mixtures prepared with PEG 4000 and PVP K30. Physicochemical characteristics of the modified crystal forms of piroxicam were investigated by X-ray powder diffractometry, FT-IR spectrophotometry and differential scanning calorimetry. Dissolution and solubility profiles of each modified crystal form were studied and compared with pure piroxicam. Solvent evaporation method (method I) produced both needle and cubic shaped crystals. Slow crystallization from ethanol with addition of PEG 4000 or PVP K30 at room temperature (method II) produced cubic crystal forms. Needle forms produced by method I improved dissolution but not solubility. Cubic crystals produced by method I had a dissolution profile similar to that of untreated piroxicam but showed better solubility than untreated piroxicam. Cubic shaped crystals produced by method II showed improved dissolution, without a significant change in solubility. Based on the XRPD results, modified piroxicam crystals obtained by method I from acetone/benzene were cube shaped, which correlates well with the FTIR spectrum modified needle forms obtained from ethanol/methanol and ethanol/acetone showed a slight shift of FTIR peak that may be attributed to differences in the internal structure or conformation.
Phosphatidylinositol 3-kinase Inhibitor (PIK75) Containing Surface Functionalized Nanoemulsion for Enhanced Drug Delivery, Cytotoxicity and Pro-apoptotic Activity in Ovarian Cancer Cells
Publisher: Springer Science and Business Media LLC
Date: 06-2012
DOI: 10.1007/S11095-012-0793-6
Abstract: Ovarian cancer is a debilitating disease, which needs multi-pronged approach of targeted drug delivery and enhanced efficacy with the use of combination therapeutics. In this study, we have examined the anticancer activity of PIK75 incorporated in surface functionalized nanoemulsions for targeted delivery to SKOV-3 cells. A pro-apoptotic molecule C(6)-ceramide was also co-delivered to augment therapeutic efficacy. EGFR and FR functionalized nanoemulsions incorporating PIK75 and C(6)-ceramide were characterized for particle size, surface charge, entrapment efficiency and morphology. Fluorescence and quantitative uptake studies were conducted in SKOV-3 cells to determine intracellular distribution. Cell viability was assessed using MTT assay while mechanism of cytotoxicity was evaluated using capsase-3/7, TUNEL and hROS assay. Cytotoxicity assay showed 57% decrease in IC(50) value of PIK75 following treatment with EGFR targeted nanoemulsion and 40% decrease following treatment with FR targeted nanoemulsion. Combination therapy with PIK75 and ceramide enhanced the cytotoxicity of PIK75 compared to therapy with in idual formulations. The increase in cytotoxicity was attributed to increase in cellular apoptosis and hROS activity. The results of this study showed that the targeted system improved cytotoxicity of PIK75 compared to the non-targeted system. Combination therapy with ceramide augmented PIK75's therapeutic activity.
Probiotics: From Functional Foods to Pharmaceutical Products
Publisher: Bentham Science Publishers Ltd.
Date: 08-2008
DOI: 10.2174/138920108785161587
Abstract: The concept of probiotics now has been around for more than a century, with its consumption increasing exponentially owing to exciting scientific and clinical findings, limiting side effects of existing pharmaceutical agents and increased consumer demand for natural products. But, the evidence for their safety and efficacy has largely been anecdotal, lacking an integrated scientific basis. Clinical studies conducted with probiotics were of inadequate design and resulted in unreliable data. That is the reason why despite having innumerable potential therapeutic uses probiotics are not being universally accepted. The purpose of present article is to amalgamate various branches of research which would help in development of "better", "commercial" and "pharmaceutical" probiotic products with defined strength, mechanism of action and indication. Probiotics have been classified into oral and vaginal in accordance to their route of administration, describing the health benefits. The article summarizes the research on significance of strain selection, interactions with co-administered agents and appropriate clinical studies uncovering the safety issues. There is a special emphasis on pharmaceutical issues including probiotic delivery systems, technological challenges during formulation, regulatory concerns, quality control and market potential. Developments in the techniques for in vitro evaluation have also been discussed.
3D Printing of Thermo-Sensitive Drugs
Publisher: MDPI AG
Date: 21-09-2021
DOI: 10.3390/PHARMACEUTICS13091524
Abstract: Three-dimensional (3D) printing is among the rapidly evolving technologies with applications in many sectors. The pharmaceutical industry is no exception, and the approval of the first 3D-printed tablet (Spiratam®) marked a revolution in the field. Several studies reported the fabrication of different dosage forms using a range of 3D printing techniques. Thermosensitive drugs compose a considerable segment of available medications in the market requiring strict temperature control during processing to ensure their efficacy and safety. Heating involved in some of the 3D printing technologies raises concerns regarding the feasibility of the techniques for printing thermolabile drugs. Studies reported that semi-solid extrusion (SSE) is the commonly used printing technique to fabricate thermosensitive drugs. Digital light processing (DLP), binder jetting (BJ), and stereolithography (SLA) can also be used for the fabrication of thermosensitive drugs as they do not involve heating elements. Nonetheless, degradation of some drugs by light source used in the techniques was reported. Interestingly, fused deposition modelling (FDM) coupled with filling techniques offered protection against thermal degradation. Concepts such as selection of low melting point polymers, adjustment of printing parameters, and coupling of more than one printing technique were exploited in printing thermosensitive drugs. This systematic review presents challenges, 3DP procedures, and future directions of 3D printing of thermo-sensitive formulations.
Daptomycin
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2015
Evaluation of a crystalline nanosuspension: Polymorphism, process induced transformation and in vivo studies
Publisher: Elsevier BV
Date: 04-2011
DOI: 10.1016/J.IJPHARM.2011.01.032
Abstract: The aim of this work was to evaluate a crystalline nanosuspension of an investigational anticancer compound, SN 30191. Solid forms of SN 30191 were prepared and characterized by thermal analysis, infrared spectroscopy, ¹³C CP/MAS SSNMR spectroscopy, SEM and powder XRD. Wet milling was performed using a high pressure homogenizer and process induced transformations were studied as a function of time and pressure using infrared spectroscopy. Dose-toxicity and pharmacokinetics (PK) of the nanocrystal formulation were evaluated in mice after intravenous administration. SN 30191 was found to exist in two polymorphic forms (I and II) and a hydrate with an equilibrium solubility < 0.1 μg/ml (pH 1.3-11.0, 37 °C). Wet milling resulted in solid state transformation as a function of pressure. Form II was found to transform into form I at intermediate pressures. A further increase in pressure resulted in formation of a hydrate. The final nanosuspension consisted of SN 30191 as a hydrate. The dose-toxicity studies revealed higher tolerance (~4 times) for the nanosuspension (10 mg/kg) when compared with a solution formulation (2.5 mg/kg). Compared with solution formulation, the nanosuspension allowed the delivery of a higher dose and rendered possible the performance of PK and tissue distribution studies in animals.
Silver based wound dressings: current issues and future developments for treating bacterial infections
Publisher: Cambridge Media
Date: 12-2020
Design and Characterization of Inulin Conjugate for Improved Intracellular and Targeted Delivery of Pyrazinoic Acid to Monocytes
Publisher: MDPI AG
Date: 22-05-2019
DOI: 10.3390/PHARMACEUTICS11050243
Abstract: The propensity of monocytes to migrate into sites of mycobacterium tuberculosis (TB) infection and then become infected themselves makes them potential targets for delivery of drugs intracellularly to the tubercle bacilli reservoir. Conventional TB drugs are less effective because of poor intracellular delivery to this bacterial sanctuary. This study highlights the potential of using semicrystalline delta inulin particles that are readily internalised by monocytes for a monocyte-based drug delivery system. Pyrazinoic acid was successfully attached covalently to the delta inulin particles via a labile linker. The formation of new conjugate and amide bond was confirmed using zeta potential, Proton Nuclear Magnetic Resonance (1HNMR) and Fourier transform infrared spectroscopy (FTIR). Scanning electron microscopy (SEM) confirmed that no significant change in size after conjugation which is an important parameter for monocyte targeting. Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) were used to establish the change in thermal properties. The analysis of in-vitro release demonstrated pH-triggered drug cleavage off the delta inulin particles that followed a first-order kinetic process. The efficient targeting ability of the conjugate for RAW 264.7 monocytic cells was supported by cellular uptake studies. Overall, our finding confirmed that semicrystalline delta inulin particles (MPI) can be modified covalently with drugs and such conjugates allow intracellular drug delivery and uptake into monocytes, making this system potentially useful for the treatment of TB.
CuS@MOF-Based Well-Designed Quercetin Delivery System for Chemo–Photothermal Therapy
Publisher: American Chemical Society (ACS)
Date: 14-09-2018
Abstract: Quercetin (QT) is one promising candidate for the treatment of various cancers with virtually no toxic side effects. However, its anticancer effect is severely restricted by its poor bioavailability, low water solubility, and chemical instability in the neutral and alkaline medium. Herein, zeolitic imidazolate framework-8 (ZIF-8) is first reported as the multifunctional nanoplatform to the codelivery of quercetin as an anticancer agent and CuS nanoparticles as a photothermal therapy (PTT) agent for synergistic combination of chemotherapy and PTT as well as overcoming the drawbacks of quercetin. Moreover, folic acid-bovine serum albumin (FA-BSA) conjugates are applied to stabilize the CuS@ZIF-8-QT to promote the bioavailability of quercetin and realize active-targeting drug delivery. Near-infrared (NIR) fluorescent imaging demonstrated the highly increased drug accumulations of FA-BSA/CuS@ZIF-8-QT in tumors, resulting from efficient internalization via FA-receptors-mediated endocytosis. The results of in vivo and in vitro anticancer experiments demonstrate that quercetin and PTT agent can work together efficiently under NIR irradiation, thus remarkably improving the anticancer effect. Therefore, our newly designed FA-BSA/CuS@ZIF-8-QT multifunctional drug delivery system might be a promising nanoplatform for cancer treatment.
Targeting of nanoparticles in cancer
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2011
Permeability issues in nasal drug delivery
Publisher: Elsevier BV
Date: 09-2002
DOI: 10.1016/S1359-6446(02)02452-2
Abstract: The nasal route is one of the most permeable and highly vascularized site for drug administration ensuring rapid absorption and onset of therapeutic action. It has been potentially explored as an alternative route for drugs with poor bioavailability and for the delivery of biosensitive and high molecular weight (MW) compounds such as proteins, peptides, steroids, vaccines, and so on. This review discusses the major factors affecting the permeability of drugs or biomolecules through the nasal mucosa, including biological, formulation and device-related factors. This information could potentially help to achieve desired plasma concentrations of drugs without compromising or altering the normal physiology of the nasal cavity.
Effect of polymer microstructure on the docetaxel release and stability of polyurethane formulation.
Publisher: Elsevier BV
Date: 04-2016
DOI: 10.1016/J.EJPB.2016.01.015
Abstract: PurSil®AL20 (PUS), a copolymer of 4,4'-dicyclohexylmethane diisocyanate (HMDI), 1,4-butane diol (BD), poly-tetramethylene oxide (PTMO) and poly-dimethyl siloxane (PDMS) was investigated for stability as a vehicle for Docetaxel (DTX) delivery through oesophageal drug eluting stent (DES). On exposure to stability test conditions, it was found that DTX release rate declined at 4 and 40 °C. In order to ulge reasons underlying this, changes in DTX solid state as well as PUS microstructure were followed. It was found that re-crystallization of DTX in PDMS rich regions was reducing the drug release at both 4 °C and 40 °C s les. So far microstructural features have not been correlated with stability and drug release, and in this study we found that at 40 °C increase in microstructural domain sizes and the inter-domain distances (from ∼85 Å to 129 Å) were responsible for hindering the DTX release in addition to DTX re-crystallization.
Polypyrrole Film as a Drug Delivery System for the Controlled Release of Risperidone
Publisher: American Institute of Physics
Date: 2009
DOI: 10.1063/1.3203241
Development and evaluation of PIK75 nanosuspension, a phosphatidylinositol-3-kinase inhibitor
Publisher: Elsevier BV
Date: 12-2012
DOI: 10.1016/J.EJPS.2012.09.015
Abstract: PIK75 is a specific inhibitor of the p110 α isoform of phosphatidylinositol-3-kinase, an enzyme which is upregulated in several human cancers. However its poor water solubility and stability has limited its pre-clinical development. In our current work we developed and evaluated PIK75 nanosuspension prepared using high pressure homogenization technique. The nanosuspension was characterized for various properties such as size, surface charge and saturation solubility. The saturation solubility processing techniques were critically evaluated to optimize s le processing conditions. In vitro studies were conducted to determine the stability of the formulation and in vivo studies were carried out to understand the pharmacokinetic and tissue distribution properties of the nanosuspension. The nanosuspension exhibited an 11-fold improvement in saturation solubility with drug recovery greater than 90% for 6h in the nanosuspension system and in human plasma. In vivo studies indicated that both PIK75 suspension and nanosuspension showed a similar plasma pharmacokinetic profile however tissue distribution studies indicated lower PIK75 levels in the kidney post nanosuspension administration. The results of this study showed that PIK75 could be formulated as a nanosuspension to improve saturation solubility, enhance stability in plasma and minimize exposure to drug metabolizing tissues.
Control of ovarian function using non-injection technologies for GnRH administration
Publisher: Elsevier BV
Date: 06-2023
Multifunctional engineered mesoporous silica/inorganic material hybrid nanoparticles: theranostic perspectives
Publisher: Elsevier BV
Date: 03-2023
Pharmacokinetics and pharmacodynamics of chlorambucil delivered in parenteral emulsion
Publisher: Elsevier BV
Date: 08-2008
DOI: 10.1016/J.IJPHARM.2008.04.027
Abstract: The aim was to assess the pharmacokinetics and anticancer activity of chlorambucil (CHL) incorporated in a parenteral emulsion (PE). A chlorambucil-loaded PE was prepared by a high energy ultrasonication method. Soybean oil was chosen as a triglyceride oil core and egg phosphatidylcholine as an emulsifier in the formulation. The particle size distribution and zeta potential were measured using Zetasizer. The results showed that the average encapsulation efficiency of chlorambucil-loaded parenteral emulsion (CHL-PE) was 98.6+/-3.2% with a particle size of 182.7+/-0.8 nm, and a zeta-potential of -37.2+/-1.1 mV. Osmolality and pH of the formulation were 305.6+/-2.3 mOsm/kg and 7.4, respectively. The chlorambucil was stable in the PE for at least 6 months stored at 4-8 degrees C. The pharmacokinetics, tissue distribution, and anticancer activity of CHL-PE and chlorambucil solution were studied after intravenous administration to C57 BL/6 male mice. CHL-PE exhibited a significantly greater AUC 0-infinity (32.4+/-0.1 microg/ml h vs. 16.9+/-0.1 microg/ml h), mean residence time (MRT) (1.32+/-0.01 h vs. 0.30+/-0.01 h), volume of distribution (409+/-15 ml/kg vs. 180+/-7 ml/kg) and elimination half-life (1.83+/-0.1h vs. 0.27+/-0.02 h) (all P<0.01), and a significantly reduced plasma clearance (309+/-16 ml/(h kg) vs. 591+/-4 ml/(h kg), P<0.01) compared to the CHL. In addition CHL-PE treatment caused significantly greater tumour growth suppression rate (% T/C) of the colon-38 adenocarcinoma in the mouse compared to CHL treatment (% T/C, 75+/-3.4% vs. 49+/-7.4%, P<0.01). These results suggest that CHL-PE could be an effective parenteral carrier for chlorambucil delivery in cancer treatment.
Immunocontraceptive activity guided fractionation and characterization of active constituents of neem (Azadirachta indica) seed extracts
Publisher: Elsevier BV
Date: 04-1998
DOI: 10.1016/S0378-8741(97)00157-8
Abstract: A novel approach for immunocontraception by intervention of local cell mediated immunity in the reproductive system by using single intrauterine application of neem oil has been described earlier. The reversible block in fertility was reported to last for 107-180 days in female Wistar rats (Upadhyay et al., 1990. Antifertility effects of neem oil by single intrauterine administration: A novel method of contraception. Proceedings Of The Royal Society Of London B 242, 175-180) and 7-11 months in monkeys (Upadhyay et al., 1994. Long term contraceptive effects of intrauterine neem treatment (IUNT) in bonnet monkeys: An alternative to intrauterine contraceptive devices. Contraception 49, 161-167). The present study, describes the identification and characterization of the biologically active fraction from neem seeds (Azadirachta indica A. Juss. Family Meliaceae), responsible for the above activity in adult female Wistar rats. Initial studies with the mechanically extracted oil and solvent extracts of neem seeds have revealed that the antifertility activity was present in constituents of low to intermediate polarity. A hexane extract of neem seeds was reported to be biologically active (Garg et al., 1994. Comparison of extraction procedures on the immunocontraceptive activity of neem seed extracts. Journal of Ethnopharmacology 22, 87-92). Subsequently, hexane extract was sequentially fractionated through the last active fraction using various separation techniques and tested for antifertility activity at each step. Preparative HPLC was used for isolating in idual components of the active fraction in quantities, sufficient for characterization. An analytical HPLC method was developed for standardization of the fraction. The active fraction was identified to be a mixture of six components, which comprises of saturated, mono and di-unsaturated free fatty acids and their methyl esters. Dose response study was performed with the last active fractions. The antifertility activity with the active fraction was reversible in nature and it was completely active until 5% concentration. There was no systemic toxic effect following the administration of the active fraction. This study, for the first time, proposes an active fraction from neem seeds, responsible for long term and reversible blocking of fertility after a single intrauterine administration with high efficacy.
Drug-Loaded, Polyurethane Coated Nitinol Stents for the Controlled Release of Docetaxel for the Treatment of Oesophageal Cancer
Publisher: MDPI AG
Date: 04-2021
DOI: 10.3390/PH14040311
Abstract: For several decades, self-expanding metal stents (SEMSs) have shown significant clinical success in the palliation of obstructive metastatic oesophageal cancer. However, these conventional oesophageal stents can suffer from stent blockage caused by malignant tumour cell growth. To overcome this challenge, there is growing interest in drug-releasing stents that, in addition to palliation, provide a sustained and localized release of anticancer drugs to minimise tumour growth. Therefore, in this study we prepared and evaluated an oesophageal stent-based drug delivery platform to provide the sustained release of docetaxel (DTX) for the treatment of oesophageal cancer-related obstructions. The DTX-loaded oesophageal stents were fabricated via dip-coating of bare nitinol stents with DTX-polyurethane (PU) solutions to provide PU coated stents with DTX loadings of 1.92 and 2.79% w/w. Mechanical testing of the DTX-PU coated stents revealed that an increase in the drug loading resulted in a reduction in the ultimate tensile strength, toughness and Young’s modulus. In vitro release studies showed a sustained release of DTX, with ~80–90% released over a period of 33 days. While the DTX-loaded stents exhibited good stability to gamma radiation sterilisation, UV sterilisation or accelerated storage at elevated temperatures (40 °C) resulted in significant DTX degradation. Cell proliferation, apoptosis and Western blotting assays revealed that the DTX released from the stents had comparable anticancer activity to pure DTX against oesophageal cancer cells (KYSE-30). This research demonstrates that the dip-coating technique can be considered as a promising approach for the fabrication of drug-eluting stents (DESs) for oesophageal cancer treatment.
pH-Responsive “Smart” Hydrogel for Controlled Delivery of Silver Nanoparticles to Infected Wounds
Publisher: MDPI AG
Date: 05-01-2021
DOI: 10.3390/ANTIBIOTICS10010049
Abstract: Persistent wound infections have been a therapeutic challenge for a long time. Current treatment approaches are mostly based on the delivery of antibiotics, but these are not effective for all infections. Here, we report the development of a sensitive pH-responsive hydrogel that can provide controlled, pH-triggered release of silver nanoparticles (AgNPs). This delivery system was designed to sense the environmental pH and trigger the release of AgNPs when the pH changes from acidic to alkaline, as occurs due to the presence of pathogenic bacteria in the wound. Our results show that the prepared hydrogel restricts the release of AgNPs at acidic pH (pH = 4) but substantially lifies it at alkaline pH (pH = 7.4 and pH = 10). This indicates the potential use of the hydrogel for the on-demand release of Ag+ depending on the environmental pH. In vitro antibacterial studies demonstrated effective elimination of both Gram-negative and positive bacteria. Additionally, the effective antibacterial dose of Ag+ showed no toxicity towards mammalian skin cells. Collectively, this pH-responsive hydrogel presents potential as a promising new material for the treatment of infected wounds.
Novel Tamoxifen Nanoformulations for Improving Breast Cancer Treatment: Old Wine in New Bottles
Publisher: MDPI AG
Date: 05-03-2020
DOI: 10.3390/MOLECULES25051182
Abstract: Breast cancer (BC) is one of the leading causes of death from cancer in women second only to lung cancer. Tamoxifen (TAM) is a hydrophobic anticancer agent and a selective estrogen modulator (SERM), approved by the FDA for hormone therapy of BC. Despite having striking efficacy in BC therapy, concerns regarding the dose-dependent carcinogenicity of TAM still persist, restricting its therapeutic applications. Nanotechnology has emerged as one of the most important strategies to solve the issue of TAM toxicity, owing to the ability of nano-enabled-formulations to deliver smaller concentrations of TAM to cancer cells, over a longer period of time. Various TAM-containing-nanosystems have been successfully fabricated to selectively deliver TAM to specific molecular targets found on tumour membranes, reducing unwanted toxic effects. This review begins with an outline of breast cancer, the current treatment options and a history of how TAM has been used as a combatant of BC. A detailed discussion of various nanoformulation strategies used to deliver lower doses of TAM selectively to breast tumours will then follow. Finally, a commentary on future perspectives of TAM being employed as a targeting vector, to guide the delivery of other therapeutic and diagnostic agents selectively to breast tumours will be presented.
Inulin and Its Application in Drug Delivery
Publisher: MDPI AG
Date: 26-08-2021
DOI: 10.3390/PH14090855
Abstract: Inulin’s unique and flexible structure, stabilization rotective effects, and organ targeting ability make it an excellent drug delivery carrier compared to other biodegradable polysaccharides. The three hydroxyl groups attached to each fructose unit serve as an anchor for chemical modification. This, in turn, helps in increasing bioavailability, improving cellular uptake, and achieving targeted, sustained, and controlled release of drugs and biomolecules. This review focuses on the various types of inulin drug delivery systems such as hydrogel, conjugates, nanoparticles, microparticles, micelles, liposomes, complexes, prodrugs, and solid dispersion. The preparation and applications of the different inulin drug delivery systems are further discussed. This work highlights the fact that modification of inulin allows the use of this polymer as multifunctional scaffolds for different drug delivery systems.
Effect of Dexamethasone and Route of Administration on Sow Farrowing Behaviours, Piglet Delivery and Litter Performance
Publisher: MDPI AG
Date: 28-03-2022
DOI: 10.3390/ANI12070847
Abstract: The inflammatory pain and stress some crated sows experience during farrowing has attendant risks of piglet-directed aggression, reduced teat exposure and hindered post-partum recovery. To counter this, the steroidal anti-inflammatory compound, dexamethasone, can be administered. To measure the potential for mucosal absorption as an alternative to injection, the permeability of porcine vaginal mucosa to dexamethasone was demonstrated using Franz cell diffusion. These studies found dexamethasone treatment diffused through vaginal mucosa at a constant rate, with 52.37 ± 5.54% permeation in 6 h. To examine in vivo effects on farrowing outcomes, dexamethasone was administered to gilts and parity one sows on the day of expected farrowing. We hypothesized that it would provide relief from farrowing discomfort and reduce behaviours threatening piglet survival. Sows were randomly assigned to receive dexamethasone as an intramuscular injection (n = 23) dexamethasone applied topically into the vagina (n = 20), or to receive no dexamethasone (n = 23). Sows (n = 66) and piglets (n = 593) were monitored for performance indicators during farrowing and early lactation. A subset of sows (n = 24) was also video monitored continuously over 24 h for behaviours associated with pain, postural changes and piglet interactions. No differences were observed between treatment for farrowing performance, piglet survival or behavioural changes for sows experiencing their first or second farrowing (p 0.05), rejecting the hypothesis that corticosteroid administration will improve sow farrowing performance. This investigation did, however, show that dexamethasone can permeate through porcine vaginal mucosa and so can be administered as a non-injectable treatment.
Development of intramammary delivery systems containing lasalocid for the treatment of bovine mastitis: Impact of solubility improvement on safety, efficacy, and milk distribution in dairy cattle
Publisher: Informa UK Limited
Date: 2015
DOI: 10.2147/DDDT.S74731
Advances in development, scale-up and manufacturing of microbicide gels, films, and tablets
Publisher: Elsevier BV
Date: 12-2010
DOI: 10.1016/J.ANTIVIRAL.2010.09.010
Abstract: Vaginal HIV microbicides are topical, self administered products designed to prevent or significantly reduce transmission of HIV infection in women. The earliest microbicide candidates developed have been formulated as coitally dependent (used around the time of sex) gels and creams. All microbicide candidates tested in Phase III clinical trials, so far, have been gel products with non-specific mechanisms of action. However, recently, research is focusing on compounds containing highly potent and specific anti-retrovirals. These specific anti-retrovirals are being formulated as primary dosage forms such as vaginal gels or in alternative dosage forms such as fast dissolve films and tablets. Recent innovations also include development of combination products of highly active antiviral drugs such as reverse transcriptase inhibitors and entry inhibitors, which would theoretically be more effective and would reduce the possibility of drug resistance. In this article, an overview of recent advances in the microbicide gel, film, and tablet formulations and issues pertaining to scale-up, formulation, and evaluation challenges and regulatory guidelines have been presented. This article forms part of a special supplement covering presentations on gels, tablets, and films from the symposium on "Recent Trends in Microbicide Formulations" held on 25 and 26 January 2010, Arlington, VA.
Active targeting co-delivery system based on pH-sensitive methoxy-poly(ethylene glycol)2K-poly(ε-caprolactone)4K-poly(glutamic acid)1K for enhanced cancer therapy
Publisher: Elsevier BV
Date: 06-2016
DOI: 10.1016/J.JCIS.2016.03.039
Abstract: In this paper, we successfully synthesized folate-modified pH-sensitive copolymer methoxy-poly(ethylene glycol)2K-poly(ε-caprolactone)4K-poly(glutamic acid)1K (mPEG2K-PCL4K-PGA1K-FA), which could form the polymeric assembly in an aqueous solution, for co-delivering hydrophilic drugs doxorubicin hydrochloride (DOX) and verapamil hydrochloride (VER) (FA-poly(DOX+VER)). Since VER was an effective P-glycoprotein inhibitor, the combination of DOX and VER could reverse the multidrug resistance efficiently and enhance the therapeutic effect. Therefore, the inhibition ratios of MCF-7/ADR resistant cancer cell treated by FA-poly (DOX+VER) were almost more than 30% higher than those of FA-polyDOX after 48h and 72h. Furthermore, the conjugation of FA could lead the co-delivery systems actively targeting into the FA receptor over-expressing cancer cells in addition to the passive accumulation of the assembly in tumor tissues. Importantly, the prepared mPEG2K-PCL4K-PGA1K-FA assembly showed high pH-sensitive property, which made the drugs mostly released in tumor tissue (acid environment) than in physiological environment (neutral environment). In summary, the as-prepared co-delivery system FA-poly(DOX+VER) demonstrated a high efficiency in reversing the multidrug resistance and targeting FA receptor to improve the anticancer effect of DOX in MCF-7/ADR resistant cells.
Harnessing the benefits of utilizing the optimal pH in conjunction with a hydrogel for wound care
Publisher: Elsevier BV
Date: 11-2023
Curcumin Can Decrease Tissue Inflammation and the Severity of HSV-2 Infection in the Female Reproductive Mucosa
Publisher: MDPI AG
Date: 04-01-2020
DOI: 10.3390/IJMS21010337
Abstract: Herpes Simplex Virus Type 2 (HSV-2) is one of the most prevalent sexually transmitted viruses and is a known risk factor for HIV acquisition in the Female Genital Tract (FGT). Previously, we found that curcumin can block HSV-2 infection and abrogate the production of inflammatory cytokines and chemokines by genital epithelial cells in vitro. In this study, we investigated whether curcumin, encapsulated in nanoparticles and delivered by various in vivo routes, could minimize inflammation and prevent or reduce HSV-2 infection in the FGT. Female mice were pre-treated with curcumin nanoparticles through oral, intraperitoneal and intravaginal routes, and then exposed intravaginally to the tissue inflammation stimulant CpG-oligodeoxynucleotide (ODN). Local intravaginal delivery of curcumin nanoparticles, but not intraperitoneal or oral delivery, reduced CpG-mediated inflammatory histopathology and decreased production of pro-inflammatory cytokines Interleukin (IL)-6, Tumor Necrosis Factor Alpha (TNF-α) and Monocyte Chemoattractant Protein-1 (MCP-1) in the FGT. However, curcumin nanoparticles did not demonstrate anti-viral activity nor reduce tissue pathology when administered prior to intravaginal HSV-2 infection. In an alternative approach, intravaginal pre-treatment with crude curcumin or solid dispersion formulations of curcumin demonstrated increased survival and delayed pathology following HSV-2 infection. Our results suggest that curcumin nanoparticle delivery in the vaginal tract could reduce local tissue inflammation. The anti-inflammatory properties of curcumin delivered to the vaginal tract could potentially reduce the severity of HSV-2 infection and decrease the risk of HIV acquisition in the FGT of women.
Development of risperidone liposomes for brain targeting through intranasal route
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.LFS.2016.08.033
Abstract: The present paper is aimed at development of functionalized risperidone liposomes for brain targeting through nasal route for effective therapeutic management of schizophrenia. The risperidone liposomes were prepared by thin film hydration method. Various parameters such as lipid ratio and lipid to drug ratio were optimized by using Design-Expert(®) Software to obtain high entrapment with minimum vesicle size. The surface of the optimized liposomes was modified by coating stearylamine and MPEG-DSPE for enhanced penetration to the brain. The formulations were evaluated for vesicle size, zeta potential, and entrapment efficiency. The morphology was studied by Transmission Electron Microscopy (TEM). In vivo efficacy was assessed by performing pharmacokinetic study in Wistar albino rats following intranasal administration of the formulations in comparison to intravenous bolus administration of pure drug. The mean vesicle size of optimized liposomes ranged from 90 to 100nm with low polydispersity index (<0.5). The entrapment efficiency of optimized liposomes was between 50 and 60%, functionalized liposomes showed maximum entrapment. The TEM images showed predominantly spherical vesicles with smooth bilayered surface. All formulations showed prolonged diffusion controlled drug release. The in vivo results showed that liposomal formulations provided enhanced brain exposure. Among the formulations studied, PEGylated liposomes (LP-16) had shown greater uptake of risperidone into the brain than plasma. High brain targeting efficiency index for LP-16 indicating preferential transport of the drug to brain. The study demonstrated successful formulation of surface modified risperidone liposomes for nasal delivery with brain targeting potential.
Targeting prostate cancer cells with hybrid elastin-like polypeptide/liposome nanoparticles
Publisher: Informa UK Limited
Date: 2018
DOI: 10.2147/IJN.S152485
Compatibility of intravenous ibuprofen with lipids and parenteral nutrition, for use as a continuous infusion
Publisher: Public Library of Science (PLoS)
Date: 03-01-2018
Identifying stakeholder opinion regarding access to “high-cost medicines”: A systematic review of the literature
Publisher: Walter de Gruyter GmbH
Date: 06-2014
DOI: 10.2478/S11536-013-0286-Y
Abstract: Objective: To identify the viewpoints and perceptions of different stakeholders regarding high cost medicines (HCMs). Methods: A systematic review of the literature was performed to identify original research articles. Using predefined categories, data related to the viewpoints of different stakeholders was systematically extracted and analyzed. Results: Thirty seven original research articles matched the criteria. The main stakeholders identified include physicians, patients, public and health funding authorities. The influence of media and other economic and ethical issues were also identified in the literature. A large number of stakeholders were concerned about lack of access to HCMs. Physicians have difficulty balancing the the rational use of expensive drugs while at the same time acting as “patients’ advocate”. Patients would like to know about all treatment options, even if they may not be able to afford them. The process and criteria for reimbursement should be transparent and access has to be equitable across patient groups. Conclusion: Access to HCMs could be improved through transparency and involvement of all stakeholders, especially patients and the public. Moral issues and the “rule of rescue” could influence decision-making process significantly. At system level, objectivity is important to ensure that the system is equitable and transparent.
The interplay between size and valence state on the antibacterial activity of sub-10 nm silver nanoparticles
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C9NA00017H
Abstract: The interplay between size and valence state in ∼3 nm silver nanoparticles resulted in the highest antibacterial effect against multi-drug resistant bacteria.
Development Pharmaceutics of Microbicide Formulations. Part II: Formulation, Evaluation, and Challenges
Publisher: Mary Ann Liebert Inc
Date: 08-2003
DOI: 10.1089/108729103322277402
Abstract: In recent years, AIDS and sexually transmitted diseases (STDs) have become a burgeoning problem and are spreading at an alarming rate. Microbicides are being developed as a new therapeutic category for prevention of transmission of sexually transmitted infections (STIs) and HIV. Many of the microbicide formulations (MF) may fail to elicit a protective response either because of a lack of efficacy or inadequate formulation. Manufacturing a stable, efficacious, safe, and optimal product is the main objective of formulation development programs. Preformulation parameters (PP), as discussed in Part I of this series, influence formulation development significantly and should be considered carefully before designing a formulation strategy. Initially, based on PP and market research, a target product profile (TPP) is generated, which defines product attributes that can be normally classified as "essential" and "desirable." A complex and dynamic process begins thereafter that takes into consideration myriad factors starting from selection of delivery system, selection of excipients, compatibility study, prototype composition, selection of process and optimization, stability testing, scale up, manufacturing under good manufacturing practices (GMP), and packaging development. Prototype formulations are evaluated for several performance characteristics (e.g., dispersion behavior, bioadhesion, retention, spreading, rheology). These compositions are also subjected to biologic evaluation by various in vitro and in vivo models. Such a well-planned, well-coordinated, and well-implemented formulation development program not only accelerates overall development but also minimizes failures in subsequent clinical development studies. The objective of this review is to highlight the importance of formulation science, outline the steps involved in this process, and explore how these can be exploited for achieving optimal MF.
Mesoporous silica nanoparticles capped with chitosan-glucuronic acid conjugate for pH-responsive targeted delivery of 5-fluorouracil
Publisher: Elsevier BV
Date: 06-2021
Early post implantation contraceptive effects of a purified fraction of neem (Azadirachta indica) seeds, given orally in rats: possible mechanisms involved
Publisher: Elsevier BV
Date: 11-1999
DOI: 10.1016/S0378-8741(99)00068-9
Abstract: Neem seed and leaf extracts have immunomodulators that induce cellular immune reactions. These aspects of neem were exploited in earlier studies, where the oral administration of the neem seed extracts in rodents and primates could completely abrogate pregnancy at an early post implantation stage. Complete restoration of fertility was observed in the animals treated in the subsequent cycles. For the purpose of using neem as a long term contraceptive, an activity guided fractionation, followed by identification and characterization of the biologically active fraction from neem seeds was carried out. Sequentially extracted fractions of neem seeds were tested orally at an early post implantation stage in rats. The hexane extract of the neem seeds was found to be biologically active and was the precursor for the final active fraction. The active fraction, identified as a mixture of six components, could completely abrogate pregnancy in rodents up to a concentration of 10%. No apparent toxic effects could be seen following treatment with the fraction. The treatment with the active fraction caused a specific activation of T lymphocyte cells of CD8+ subtype as well as phagocytic cells followed by elevation in cytokines gamma-interferon and TNF. The results of the present study show that a pure active fraction of neem seeds could be obtained for the purpose of early post implantation contraception when given orally, and its mechanism of action seems to be by activating cell mediated immune reactions.
Evaluation of degradation kinetics for abamectin in formulations using a stability indicating method
Publisher: Walter de Gruyter GmbH
Date: 03-2013
Abstract: The aim of this study was to evaluate stability characteristics and kinetics behavior of abamectin (ABM) as a 1 % (m/V) topical veterinary solution. During the study, s les stressed at 55 and 70 °C were regularly analyzed for several parameters over 8 weeks on a chromatographic (HPLC) system, using a Prodigy C18, 250 x 4.6 mm, 5-μm, column eluting with 15 : 34 : 51 (V/V/V) water/methanol/ acetonitrile as mobile phase. The HPLC method was validated for precision, accuracy, linearity and specificity, and was found to be stability indicating. The results showed that degradation of ABM followed first-order kinetics and data on loss in kobs (s-1) and half life (t1/2, days) demonstrated ABM showing the maximum stability in glycerol formal. The degradation behavior of ABM varies from solvent to solvent. The effect of added alkali on pH change and loss of ABM was studied and found to be unique for all solvents and very distinct from typical hydrolysis degradation. The present study may serve as a platform to design and develop topical non-aqueous solutions of ABM for veterinary use given no such comprehensive efforts have been published to date on the stability profile of ABM in non-aqueous solvents.
Migrant health in New Zealand: exploring issues concerning medicines access and use
Publisher: Oxford University Press (OUP)
Date: 07-11-2012
DOI: 10.1111/J.1759-8893.2012.00105.X
Abstract: Every year a cohort of new migrants enters New Zealand (NZ), bringing challenges that impact on medicines use and health outcomes. The prescribing of medicines is a common therapeutic intervention and access to medicines and optimal use cannot be assumed for these populations. Internationally the literature exploring issues relating to medicines access and use by migrants in high-income countries is scarce. This study aims to explore attitudes, beliefs and perceptions of a cohort of migrants about medicines access and use in NZ. A qualitative research methodology was employed with participants being recruited through snowballing techniques and interviewed (seven Indian and four Chinese). Following consent, a semi-structured guide was used for discussions. Themes were developed from codes based on the guide. These themes were developed by two members of the research team and reviewed by a third member. Emergent themes reflected the following dialogue: (a) financial barriers: paying doctor and pharmacist, lack of affordability of over-the-counter medicines, sharing medicines with family and friends (b) information transfer and knowledge of rules, systems and initiatives, particularly regarding subsidies and brand switching (c) misconceptions due to culture and language barriers, including not understanding information and lack of compliance in symptom-free disease (d) perceptions of high quality in prescription medicines (e) non-disclosure of traditional medicine use and (f) variability of community pharmacy service provision, especially counselling. Significant barriers to access and optimal use of medicines by new migrants in NZ were identified. Policy change and educational interventions are likely to be required to improve medicines-related health care to migrant New Zealanders. Future research will need to quantify the extent of the issues and interventions should be developed and evaluated as ongoing research.
BigFooT: A robust optimal-latency BFT blockchain consensus protocol with dynamic validator membership
Publisher: Elsevier BV
Date: 02-2022
Docetaxel epimerization in silicone films: A case of drug excipient incompatibility
Publisher: Wiley
Date: 11-02-2014
DOI: 10.1002/DTA.1617
Abstract: Docetaxel (DTX) is an anti-cancer compound derived from 10-deacetyl baccatin III which is indicated for treatment of breast, lung, prostate, gastro-esophageal, and head and neck cancers. Epimerization of DTX at the C-7 hydroxyl position has intrigued chemists and has been implicated in loss of potency, as well as in the development of resistance in tumour cells. For localized controlled delivery of this agent, silicone films were prepared from a commercially available silicone kit. High levels of epimeric degradants were unexpectedly found in the in vitro release media. Herein, we discuss this anomalous DTX degradation to epimeric impurities, and discuss the possible reasons for degradation. Systematic stability studies were performed on the release media and the silicone kit components. It was found that release media and tin-based catalyst present in the silicone kit could be responsible for the epimeric conversion. This unusual case of chemical incompatibility can affect product performance and can even lead to development of resistance in tumour cells towards DTX.
Development of a novel oral delivery system of edaravone for enhancing bioavailability
Publisher: Elsevier BV
Date: 12-2017
DOI: 10.1016/J.IJPHARM.2016.10.052
Abstract: Edaravone (EDR), a strong free radical scavenger, is known for its promising therapeutic potential in oxidative stress (OS) associated diseases, however poor oral bioavailability is the major obstacle in its potential use. Oral liquid dosage form is the most preferred delivery method in paediatric, geriatric and specialised therapies. The present research discusses the development of a Novel Oral Delivery System (NODS) of EDR to enhance oral bioavailability. From preformulation study, solubility, and stability were identified as key challenges and the requirement of an acidic environment and protection against oxidation were found to be critical. The NODS made up of a mixture of Labrasol (LBS) and an acidic aqueous system, was optimized on the basis of solubility and stability study. It can be stored ≤40°C for at least one month. Drug release from NODS was slow, sustained and significantly better as compared to suspension. The significant reduction in metabolism and improvement in permeability across the small intestine were observed with NODS compared to free EDR. The oral pharmacokinetic study showed 571% relative bioavailability with NODS compared to EDR suspension. From the results obtained, NODS is a promising candidate for use in OS associated diseases.
Solid Self-Nano Emulsifying Nanoplatform Loaded with Tamoxifen and Resveratrol for Treatment of Breast Cancer
Publisher: MDPI AG
Date: 18-07-2022
DOI: 10.3390/PHARMACEUTICS14071486
Abstract: The solid self-nanoemulsifying drug delivery system (s-SNEDDS) is a growing platform for the delivery of drugs via oral route. In the present work, tamoxifen (TAM) was loaded in SNEDDS with resveratrol (RES), which is a potent chemotherapeutic, antioxidant, anti-inflammatory and P-gp inhibitor for enhancing bioavailability and to obtain synergistic anti-cancer effect against breast cancer. SNEDDS were developed using capmul MCM as oil, Tween 80 as surfactant and transcutol-HP as co-surfactant and optimized by central composite rotatable design. Neusilin US2 concentration was optimized for adsorption of liquid SNEDDS to prepare s-SNEDDS. The developed formulation was characterized and investigated for various in vitro and cell line comparative studies. Optimized TAM-RES-s-SNEDDS showed spherical droplets of a size less than 200 nm. In all in vitro studies, TAM-RES-s-SNEDDS showed significantly improved (p ˂ 0.05) release and permeation across the dialysis membrane and intestinal lumen. Moreover, TAM-RES-s-SNEDDS possessed significantly greater therapeutic efficacy (p 0.05) and better internalization on the MCF-7 cell line as compared to the conventional formulation. Additionally, oral bioavailability of TAM from SNEDDS was 1.63 folds significantly higher (p 0.05) than that of combination suspension and 4.16 folds significantly higher (p 0.05) than TAM suspension. Thus, findings suggest that TAM- RES-s-SNEDDS can be the future delivery system that potentially delivers both drugs to cancer cells for better treatment.
Combining the potential of 3D printed buccal films and nanostructured lipid carriers for personalised cannabidiol delivery
Publisher: Springer Science and Business Media LLC
Date: 30-10-2023
Assemblies for In Vitro Measurement of Bioadhesive Strength and Retention Characteristics in Simulated Vaginal Environment
Publisher: Informa UK Limited
Date: 2002
Abstract: The vaginal route of administration offers a promising option for local and systemic delivery of drugs. Conventional vaginal formulations are associated with limitations of poor retention, leakage, and messiness, thereby causing inconvenience to users. To overcome these limitations, formulations that adhere to the vaginal mucosa for a sufficient period of time need to be developed. Bioadhesion and retention are desirable characteristics of a vaginal formulation to achieve desired efficacy. These properties can be built in during formulation development by the use of bioadhesive polymers. In the present study, assemblies for in vitro measurement of bioadhesive strength and retention characteristics of vaginal formulations have been developed. A modified simulated vaginal fluid (SVFM) was used to simulate vaginal conditions for bioadhesion studies. Cellophane hydrated with SVFM and isolated sheep vaginal mucosa were used as model membranes. The bioadhesive potential of various polymers and their combinations was evaluated. Among the polymers evaluated, xanthan gum (XG), sodium alginate (SA), Polycarbophil (PC), and their combinations (XG + SA and XG + PC) were found to possess significant bioadhesive strength. In retention experiments, XG, SA, and combinations (XG + SA and XG + PC) were retained in isolated sheep vaginal tissue, while PC exhibited poor retention under experimental conditions. Based on the results of the study conducted, XG, SA, and combinations (XG + SA and XG + PC) have been proposed as potential candidates for developing bioadhesive vaginal drug delivery systems.
Development and Characterization of Bioadhesive Vaginal Films of Sodium Polystyrene Sulfonate (PSS), a Novel Contraceptive Antimicrobial Agent
Publisher: Springer Science and Business Media LLC
Date: 04-2005
DOI: 10.1007/S11095-005-2490-1
Abstract: Polystyrene sulfonate (PSS) is a novel noncytotoxic antimicrobial contraceptive agent. A gel formulation of PSS was found safe for vaginal administration in phase I clinical trials. The purpose of the current study was to develop and evaluate novel bioadhesive vaginal film formulations of PSS. PSS films were prepared by solvent evaporation and optimized for various physical, mechanical, and aesthetic properties. Further, films were evaluated for various biological activities and safety. Vaginal films containing 300 mg PSS per unit have been developed, using generally regarded as safe (GRAS) listed excipients. The films are colorless, transparent, thin, soft, and tough, dissolve rapidly in physiologic fluid to form a smooth, viscous and bioadhesive solution that could be retained in the vagina for prolonged intervals. Sperm function inhibition (hyaluronidase and cervical mucus penetration) and antimicrobial activities against human immunodeficiency virus (HIV) and herpes simplex virus (HSV) by PSS films were found comparable to PSS. Also, films did not inhibit normal vaginal microflora (Lactobacillus) and were noncytotoxic as indicated by negligible sperm immobilization and cytotoxicity to host cell assays. Rapidly dissolving bioadhesive vaginal film formulation of PSS with desired physical, mechanical, aesthetic, and biological properties is a suitable candidate vaginal microbicide for prevention of sexually transmitted disease (STDs) and is ready for toxicological and clinical evaluation.
Development of Solid Dispersion Systems of Dapivirine to Enhance its Solubility
Publisher: Bentham Science Publishers Ltd.
Date: 05-2013
DOI: 10.2174/1567201811310030007
Abstract: Dapivirine, formerly known as TMC 120, is a poorly-water soluble anti-HIV drug, currently being developed as a vaginal microbicide. The clinical use of this drug has been limited due to its poor solubility. The aim of this study was to design solid dispersion systems of Dapivirine to improve its solubility. Solid dispersions were prepared by solvent and fusion methods. Dapivirine release from the solid dispersion system was determined by conducting in-vitro dissolution studies. The physicochemical characteristics of the drug and its formulation were studied using Differential Scanning Calorimetry (DSC), powder X-ray Diffraction (XRD), Fourier-transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM). A significant improvement in drug dissolution rate was observed with the solid dispersion systems. XRD, SEM and DSC results indicated the transformation of pure Dapivirine which exists in crystalline form into an amorphous form in selected solid dispersion formulations. FTIR and HPLC analysis confirmed the absence of drug-excipient interactions. Solid dispersion systems can be used to improve the dissolution rate of Dapivirine. This improvement could be attributed to the reduction or absence of drug crystallinity, existence of drug particles in an amorphous form and improved wettability of the drug.
Interpolymer Complexation and its Effect on Bioadhesive Strength 6 Dissolution Characteristics of Buccal Drug Delivery Systems
Publisher: Informa UK Limited
Date: 1994
Scale‐up and Postapproval Changes (SUPAC) Regulations
Publisher: Wiley
Date: 28-08-2007
Properties of a new acid-buffering bioadhesive vaginal formulation (ACIDFORM)
Publisher: Elsevier BV
Date: 07-2001
DOI: 10.1016/S0010-7824(01)00217-7
Abstract: Vaginal prophylactic methodology may prevent heterosexual transmission of the HIV and other sexually transmitted disease-causing organisms as well as unplanned pregnancies. A new delivery system (ACIDFORM) was designed with acid-buffering, bioadhesive, and viscosity-retaining properties to (1) maintain the acidic vaginal milieu (the low pH inactivates many pathogens and spermatozoa), (2) form a protective layer over the vaginal/cervical epithelium (minimizing contact with pathogenic organisms), and (3) provide long-term vaginal retention. A Phase I clinical study with ACIDFORM provided initial information about its safety and showed the formation of a layer over the vaginal/cervical epithelium [1 Amaral et al., Contraception 1999 :361-6]. To study the properties of the gel (without active ingredient) in more detail, ACIDFORM's acid-buffering, bioadhesive, viscosity-retaining, and spermicidal properties were compared in vitro to marketed formulations, and its long-term stability was assessed. ACIDFORM, either when titrated with NaOH or when mixed directly with semen, is highly acid buffering and much more effective than Aci-Jel, a commercial acid-buffering vaginal product. ACIDFORM adheres well to two model membranes (excised sheep vagina and cellophane) and is more bioadhesive than Conceptrol, Advantage S, Replens, Aci-Jel, and K-Y jelly. On dilution, ACIDFORM also retains its viscosity better than these marketed products. ACIDFORM is spermicidal and is stable for at least 2 years. These results suggest that ACIDFORM has advantages over presently marketed vaginal delivery systems. The gel may either be useful by itself as an antimicrobial contraceptive product or as a formulation vehicle for an active ingredient with antimicrobial and/or contraceptive properties.
Selection of excipients for extended release formulations of glipizide through drug–excipient compatibility testing
Publisher: Elsevier BV
Date: 07-2005
DOI: 10.1016/J.JPBA.2005.02.026
Abstract: For the development of extended release formulations of glipizide, techniques of thermal and isothermal stress testing (IST) were used to assess the compatibility of glipizide with selected excipients. Initially, differential scanning calorimeter (DSC) was used to evaluate the compatibility. IR spectrum of drug-excipient mixture was also compared with that of pure drug and excipient. Compatibility of excipients defined in the prototype formula was tested using IST. Based on the DSC results alone, magnesium stearate, meglumine, TRIS buffer, and lactose, were found to exhibit interaction with glipizide. Stressed binary mixtures (stored at 50 degrees C for 3 weeks) of glipizide and meglumine showed yellow coloration indicating potential incompatibility. Based on the results of DSC, IR, and/or HPLC, excipients defined in the prototype formula were found to be compatible with glipizide. The optimized formulation developed using the compatible excipients were found to be stable after 3 months of accelerated stability studies (40 degrees C and 75% RH). Overall, compatibility of excipients with glipizide was successfully evaluated using the combination of thermal and IST methods and the formulations developed using the compatible excipients was found to be stable.
Understanding the Effect of Functionalization on Loading Capacity and Release of Drug from Mesoporous Silica Nanoparticles: A Computationally Driven Study
Publisher: American Chemical Society (ACS)
Date: 04-03-2022
In vitro Antimicrobial Activity of Robenidine, Ethylenediaminetetraacetic Acid and Polymyxin B Nonapeptide Against Important Human and Veterinary Pathogens
Publisher: Frontiers Media SA
Date: 25-04-2019
Eradication of Mature Bacterial Biofilms with Concurrent Improvement in Chronic Wound Healing Using Silver Nanoparticle Hydrogel Treatment
Publisher: MDPI AG
Date: 08-09-2021
DOI: 10.3390/BIOMEDICINES9091182
Abstract: Biofilm-associated infections are a major cause of impaired wound healing. Despite the broad spectrum of anti-bacterial benefits provided by silver nanoparticles (AgNPs), these materials still cause controversy due to cytotoxicity and a lack of efficacy against mature biofilms. Herein, highly potent ultrasmall AgNPs were combined with a biocompatible hydrogel with integrated synergistic functionalities to facilitate elimination of clinically relevant mature biofilms in-vivo combined with improved wound healing capacity. The delivery platform showed a superior release mechanism, reflected by high biocompatibility, hemocompatibility, and extended antibacterial efficacy. In vivo studies using the S. aureus wound biofilm model showed that the AgNP hydrogel (200 µg/g) was highly effective in eliminating biofilm infection and promoting wound repair compared to the controls, including silver sulfadiazine (Ag SD). Treatment of infected wounds with the AgNP hydrogel resulted in faster wound closure (46% closure compared to 20% for Ag SD) and accelerated wound re-epithelization (60% for AgNP), as well as improved early collagen deposition. The AgNP hydrogel did not show any toxicity to tissue and/or organs. These findings suggest that the developed AgNP hydrogel has the potential to be a safe wound treatment capable of eliminating infection and providing a safe yet effective strategy for the treatment of infected wounds.
High surface area polypyrrole scaffolds for tunable drug delivery
Publisher: Elsevier BV
Date: 02-2013
DOI: 10.1016/J.IJPHARM.2013.01.006
Abstract: Intrinsically conducting polymers such as polypyrrole (PPy) are viable platforms for efficient drug delivery, where release rates can be tuned by external electrical stimulus. In this study, the successful fabrication of 3-dimensionally ordered macroporous PPy inverse opal thin films is described, and the viability of such films for controlled drug release evaluated in vitro. The PPy inverse opal thin films were obtained by electropolymerization of PPy through the interstitial voids of a colloidal crystal template composed of poly(methyl methacrylate) colloids of diameter ∼430 nm. Chemical etching of the template yielded macroporous PPy inverse opal scaffolds. The model drug risperidone was loaded into the PPy inverse opal films, and then entrapped by electropolymerization of a non-porous PPy overlayer. The morphology and chemical composition of the PPy scaffolds were evaluated by SEM and FTIR spectroscopy, respectively. The high surface area PPy inverse opal scaffolds exhibited enhanced drug loading and releasing capabilities compared to conventional non-porous PPy films. Drug release profiles could be modified by applying electrical stimulus, which caused actuation of the porous polypyrrole films. The proposed delivery system may find use as an implantable device where drug release can be electrically tuned according to patient requirements.
Mucoadhesive Buccal Film of Estradiol for Hormonal Replacement Therapy: Development and In-Vivo Performance Prediction
Publisher: MDPI AG
Date: 28-02-2022
DOI: 10.3390/PHARMACEUTICS14030542
Abstract: The age-related loss of circulating estrogen that occurs during the menopausal transition manifests itself through a variety of symptoms including vasomotor (hot flushes and night sweats), genito-urinary syndrome (vaginal dryness and urinary symptoms), sexual dysfunction, mood, and sleep disturbance that often last longer than a decade. Furthermore, reductions in estrogen level increase the risks of chronic complications such as osteoporosis, cardiovascular disease, and cognitive decline among others, thereby affecting the quality of life of women. Although oral estrogens are the most widely used therapy for menopausal symptoms, they suffer from poor bioavailability, and there are concerns over their safety, creating a significant concern to consumers. Mucoadhesive buccal films are an innovative dosage form that offers several advantages including avoidance of the first-pass metabolism, fast onset of action, and importantly, improved patient acceptance. In the current work, we developed mucoadhesive estradiol film for hormonal replacement therapy using film-forming polymers. Two approaches, namely, co-solvency and nano-emulsion were evaluated to increase solubility and hence incorporate estradiol, a poorly water-soluble drug, into a formulation made from the hydrophilic polymer/s. The films were characterised for their mechanical and physicochemical properties. In-vitro release study showed that about 80% of the drug was released within 6 min from films prepared by the nano-emulsion approach, whereas it took about 10.5 min to get similar drug release from films prepared by the co-solvency approach. The ex-vivo permeation result indicates that about 15% of the drug permeated across the porcine buccal mucosa in the first 10 h from films prepared by the nano-emulsion approach, while permeation across porcine buccal mucosa was only observed at around 24 h from films prepared by the co-solvency method. The nano-emulsion films were evaluated for in vivo performance using a convolution technique using R software. The predicted Cmax and Tmax were found to be 740.74 ng mL−1 and 7 min, respectively, which were higher than previously reported in vivo concentration from oral tablets. The results demonstrated that mucoadhesive film of estradiol based on the nano-emulsion approach could be a promising platform for the delivery of estradiol through the buccal mucosa for the treatment of menopausal symptoms.
Investigation of the biodistribution, breakdown and excretion of delta inulin adjuvant
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.VACCINE.2017.06.045
Abstract: Insoluble, nanostructured delta inulin particles enhance the immunogenicity of co-administered protein antigens and consequently are used as a vaccine adjuvant (Advax™). To better understand their immunomodulatory properties, the in vitro hydrolysis and in vivo distribution of delta inulin particles were investigated. Delta inulin particle hydrolysis under bio-relevant acidic conditions resulted in no observable change to the bulk morphology using SEM, and HPLC results showed that only 6.1% of the inulin was hydrolysed over 21days. However, 65% of the terminal glucose groups were released, showing that acid hydrolysis relatively rapidly releases surface bound chemistries. This was used to explain in vivo biodistribution results in which delta inulin particles surface-labelled with fluorescein-5-thiosemicabizide were administered to mice using intramuscular (I.M.) or subcutaneous (S.C.) routes. Comparison analysis of the fluorescence of soluble inulin in the supernatants of homogenised tissues maintained at room temperature or heated to 100°C to solubilise particulate inulin was used to distinguish between fluorescent probe on soluble inulin and probe bound to inulin within particles. Following both I.M. and S.C. injection delta inulin exhibited a depot behaviour with local injection site residence for several weeks. Over this time, as injection site inulin reduced, there was measurable transport of intact delta inulin particles by macrophages to secondary lymphoid organs and the liver. Ultimately, the injected delta inulin became solubilised resulting in its detection in the plasma and in the urine. Thus injected delta inulin particles are initially taken up by macrophages at the site of injection, trafficked to secondary lymphoid tissue and the liver, and hydrolysed resulting in their becoming soluble and diffusing into the blood stream, from whence they are glomerularly filtered and excreted into the urine. These results provide important insights into the biodistribution of I.M. or S.C. injected delta inulin particles when used as vaccine adjuvants and their method of excretion.
Co-delivery of doxorubicin hydrochloride and verapamil hydrochloride by pH-sensitive polymersomes for the reversal of multidrug resistance
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C5RA15313A
Abstract: A promising co-delivery system was proposed for effectively reversing multidrug resistance of cancer cells and simultaneously improving the anticancer effect of the drug.
Advances in the Use of Anti-inflammatory Agents to Manage Chemotherapy-induced Oral and Gastrointestinal Mucositis
Publisher: Bentham Science Publishers Ltd.
Date: 13-07-2018
DOI: 10.2174/1381612824666180409093918
Abstract: Mucositis is a side effect associated with the use of chemotherapy, and has a significant impact on the quality of life. Mucositis, by definition, refers to the inflammation of the mucosa and occurs throughout the alimentary tract from the mouth to anus. Nuclear Factor kappa B (NFκB) encompasses a family of transcription factors, which upregulate pro-inflammatory cytokines. These are recognized as key targets in developing therapeutic interventions for chemotherapy-induced mucositis, and cyclooxygenase (COX)-2 inhibition may also be beneficial in reducing the severity and duration. This review focuses on the pathobiology of chemotherapy-induced oral and gastrointestinal mucositis and recent research examining the role of agents with anti-inflammatory activity in treatment and prevention of the condition. We consider agents in clinical use as well as some others under current investigation including plant-derived and other natural medicines.
Study of the vaginal tolerance to acidform, an acid-buffering, bioadhesive gel
Publisher: Elsevier BV
Date: 12-1999
DOI: 10.1016/S0010-7824(99)00102-X
Abstract: Vaginal tolerance tests were performed with a new potential microbicidal and spermicidal product, an acid-buffering vaginal gel (Acidform) without or with nonoxynol-9 (N-9). The potential advantages over other vaginal products include keeping a low pH, decrease of the irritating effect of N-9 on the cervix or vaginal mucosa associated with greater retention of the product after application, and decreasing "messiness" as compared to other vaginal products. Three groups of six women were admitted and randomly assigned to use Acidform with 0%, 2.5%, and 5% N-9. Colposcopic evaluation for vulvar, vaginal, and cervical signs of irritation was performed and photographs were taken, following a specific World Health Organization protocol, at time 0, and after 24 h and 6 days of application of the gel. No irritation or symptom was reported by users of Acidform without N-9. A generalized and intense erythema in cervix was observed in 10 of 12 Acidform/N-9 users and abrasion occurred in nine of them. Vulvar irritation was seen in seven of these 10 volunteers. N-9 concentration in the gel (2.5% or 5.0%) was not related to the findings. No ulcer, exulceration, or de-epithelialization was observed. Acidform without N-9 was well tolerated by volunteers, but it was unable to protect the cervix, vagina, and vulva from the N-9 effects.
Flow cytometric assessment of the protectants for enhanced in vitro survival of probiotic lactic acid bacteria through simulated human gastro-intestinal stresses
Publisher: Springer Science and Business Media LLC
Date: 04-04-2012
DOI: 10.1007/S00253-012-4030-3
Abstract: The aim of this study was to apply flow cytometric (FCM) analysis to assess the use of sucrose and lecithin vesicles for the protection of probiotic lactic acid bacteria in response to the challenge of gastric acidity and bile salts. FCM analysis in combination with fluorescent probes carboxyfluorescein (cF) and propidium iodide was used to reveal the physiological heterogeneity in the stressed bacteria population. Three subpopulations (intact, stressed, and damaged) were differentiated by FCM in all six examined strains. Significant changes were observed in the presence of the selected protectants. The addition of 20 mM sucrose in the simulated gastric fluid substantially increased the number of intact cells over 20 folds and reduced the damaged subpopulation by half. The presence of 2 % (w/v) lecithin vesicles was shown to protect 50 % more intact cells from the challenge of bile salts. The improved survival as evaluated by FCM analysis was further assessed for the proliferation capacity by sorting a number of cells from each subpopulation on nutrient agar plate. The result confirmed conformity between the proliferation-based cultivability and the probe-indicated viability in the s les of the intact and the damaged subpopulations. However, it also revealed the complexities of the stressed (injured) subpopulation. In conclusion, FCM analysis confirmed that the selected protectants could improve the survival of the probiotic strains in the simulated GI environments. The FCM analysis also proved to be a useful analytical tool for the probiotics research.
A Birth Control Vaccine is on the Horizon for Family Planning
Publisher: Informa UK Limited
Date: 1993
DOI: 10.3109/07853899309164169
Abstract: Vaccines for control of fertility are likely to have an important impact on family planning methods. They are designed to act by mobilization of an internal physiological process and do not require external medication on a continuous basis. A number of birth control vaccines are at different stages of development, the most advanced being a vaccine inducing antibodies against human chorionic gonadotrophin (hCG). This vaccine consists of a heterospecies dimer (HSD, beta hCG associated with alpha-subunit of ovine luteinizing hormone, beta hCG:alpha oLH) linked to tetanus toxoid (TT) or diphtheria toxoid (DT) as carriers. The vaccine has recently passed an important milestone it has completed the first leg of phase II efficacy trials. Women of proven fertility leading active sexual life were protected from becoming pregnant at antibody titres > or = 50 ng of hCG bioneutralization capacity per ml. This vaccine has previously been demonstrated to be reversible in its effect. It is free from any notable side-effects on endocrine, cardiovascular and other body functions. Ovulation was not disturbed and menstrual regularity was maintained. A logistic disadvantage of the present vaccine is the requirement for multiple injections. This is expected to be overcome by encapsulation of the requisite doses of the vaccine in biodegradable microspheres, which could be given at a single contact point for sustained antibody titres lasting over a year. A live recombinant vaccine has also been made that elicits high anti-hCG titres in monkeys for nearly 2 years following primary immunization and a booster at 8-9 months.
Concept Design, Development and Preliminary Physical and Chemical Characterization of Tamoxifen-Guided-Mesoporous Silica Nanoparticles
Publisher: MDPI AG
Date: 04-01-2021
DOI: 10.3390/MOLECULES26010219
Abstract: Conventional chemotherapies used for breast cancer (BC) treatment are non-selective, attacking both healthy and cancerous cells. Therefore, new technologies that enhance drug efficacy and ameliorate the off-target toxic effects exhibited by currently used anticancer drugs are urgently needed. Here we report the design and synthesis of novel mesoporous silica nanoparticles (MSNs) equipped with the hormonal drug tamoxifen (TAM) to facilitate guidance towards estrogen receptors (ERs) which are upregulated in breast tumours. TAM is linked to the MSNs using a poly-ʟ-histidine (PLH) polymer as a pH-sensitive gatekeeper, to ensure efficient delivery of encapsulated materials within the pores. XRD, HR-TEM, DLS, SEM, FT-IR and BET techniques were used to confirm the successful fabrication of MSNs. The MSNs have a high surface area ( m2/g) and a mean particle size of 150 nm, which is an appropriate size to allow the penetration of premature blood vessels surrounding breast tumours. Successful surface functionalization was supported by FT-IR, XPS and TGA techniques, with a grafting ratio of approximately 29%. The outcomes of this preliminary work could be used as practical building blocks towards future formulations.
Recent progress of targeted nanocarriers in diagnostic, therapeutic, and theranostic applications in colorectal cancer
Publisher: Elsevier BV
Date: 10-2023
Evaluation of vitamin D medicines and dietary supplements and the physicochemical analysis of selected formulations
Publisher: Springer Science and Business Media LLC
Date: 27-07-2012
DOI: 10.1007/S12603-012-0090-4
Abstract: Vitamin D is purported to offer wide ranging and numerous health benefits leading to increased interest from manufacturers of medicines and dietary supplements. Elderly patients frequently require vitamin D supplementation due to reduced sun exposure and dietary intake. There are ever increasing numbers of vitamin D formulations in the global market. However, due to a lack of regulatory restrictions for some of these products the quality of these dosage forms can be of some concern. To study vitamin D formulations available in the global market and evaluate physic-chemical properties of selected formulations from the New Zealand market. The first component of this study consisted of a search for different vitamin D formulations available in selected countries. The second component of the study involved assaying selected vitamin D formulations available in New Zealand. Vitamin D was extracted from capsule, tablet and emulsion formulations and quantified using a validated High Performance Liquid Chromatography (HPLC) method. Of the 14 analysed formulations, only 60% were within 100±10 % of the label claim. The two registered, prescription formulations available exhibited vitamin D levels of 90±4% and 97±2% of the labeled amount, while non-registered, non-prescription dietary supplements had vitamin D levels ranging from 8±2% to 201±29% of the labeled amount. Dietary supplements do not require strict regulation and showed a large variation in the percentage label claim of vitamin D. Prescription formulations which are more strictly regulated gave content values within standard acceptance ranges. Vitamin D has proven health benefits and also the potential to cause harm, therefore there is a need for tougher regulations of dietary supplements to ensure acceptable quality.
Evaluation of policies to support drug development in New Zealand
Publisher: Elsevier BV
Date: 07-2010
DOI: 10.1016/J.HEALTHPOL.2010.01.012
Abstract: Changes in the traditional model of drug development are creating a potential opportunity for New Zealand's drug development industry. This research evaluates whether New Zealand could utilise some of the policies employed by countries with successful drug development industries. A framework to support a drug development industry was developed by taking into account policies that affect the industry. The framework was then used to analyse the types of policies provided by different countries and to postulate six different models that support a pharmaceutical industry. Countries with a successful drug development industry have identified their strengths, analysed the opportunities in the industry, and have employed consistent and specific policies in support of their industry. New Zealand's policy in support of its drug development industry is most similar to that of the medical research-based model of the UK, Australia and Canada. New Zealand needs to develop a consistent policy for support of its drug development industry based on identifying and focussing on the competencies where it is internationally competitive. A strong partnership with Australia could capitalise on the strengths of both countries and linkages with other Asia-Pacific countries could further promote the region's capabilities in drug development research.
Isolation and characterization of degradation products of moxidectin using LC, LTQ FT-MS, H/D exchange and NMR
Publisher: Springer Science and Business Media LLC
Date: 18-09-2012
DOI: 10.1007/S00216-012-6393-9
Abstract: This study aimed to evaluate the degradation profile and pathways, and identify unknown impurities of moxidectin under stress conditions. During the experiments, moxidectin s les were stressed using acid, alkali, heat and oxidation, and chromatographic profiles were compared with known impurities given in European Pharmacopeia (EP) monograph. Moxidectin has shown good stability under heat, while reaction with alkali produced 2-epi and ∆2,3 isomers (impurities D and E in EP) by characteristic reactions of the oxahydrindene (hexahydrobenzofuran) portion of the macrocyclic lactone. Two new, previously unreported, unknown degradation products, i.e. impurity 1 and impurity 2, detected after acid hydrolysis of moxidectin (impurity 2 was also observed to a lesser extent after oxidation), were isolated from s le matrices and identified using liquid chromatography, NMR, high-resolution FT-ICR MS, and hydrogen/deuterium exchange studies. FTMS analysis showed accurate mass of molecular ion peaks for moxidectin at m/z 640.38412, impurity 1 at m/z 656.37952 and impurity 2 at m/z 611.35684, giving rise to daughter ions traceable up to the seventh levels of MS(n) experiments and supporting the proposed structures. Both unknown impurities along with moxidectin were fully characterized by (1)H, (13)C, 1D HMBC and 2D (NOESY, COSY and HSQC) NMR experiments. The interpretation of experimental data positively identified impurity 1 as 3,4-epoxy-moxidectin and impurity 2 as 23-keto-nemadectin. The identification of new impurities and correlation of their chromatographic profiles with the EP method is very useful to establish the stability profile of moxidectin and its preparations, as well as add value to the forthcoming moxidectin finished product European Pharmacopeia monographs.
A validated high performance liquid chromatographic method for analysis of isosorbide mononitrate in bulk material and extended release formulations
Publisher: Elsevier BV
Date: 10-2002
DOI: 10.1016/S0731-7085(02)00317-5
Abstract: A reversed phase HPLC method using C(18) column was developed for the quantitative determination of isosorbide mononitrate (IMN) in the bulk material and extended release dosage forms. The method was specific to IMN and able to resolve the drug peak from the pharmacopoeial impurities and formulation excipients. The method was accurate, precise, and linear within the desired range. In addition to analysis of assay and dissolution s les, the method was successfully used for analysis of drug-excipient compatibility s les of IMN used for development of extended release formulations in our laboratory and their subsequent stability studies. The method was also used for analysis of IMN in commercially available raw material.
Development Pharmaceutics of Microbicide Formulations. Part I: Preformulation Considerations and Challenges
Publisher: Mary Ann Liebert Inc
Date: 2003
DOI: 10.1089/108729103321042881
Abstract: Microbicides, the compounds and formulations that can prevent transmission of sexually transmitted diseases (STDs)/HIV are being pursued actively as a promising AIDS intervention. The drug development chain for a topical microbicide differs significantly from that of any systemic or topical compound/formulation regarding to time line, cost, activities, and milestones. This is in part because of the lack of standard in vitro models to assess efficacy, and complex ethical issues in clinical trials of microbicides. Several factors, including changes in the physiology of the cervix and vagina with age and menstrual cycle, intercourse, as well as leakage of the formulation from the vagina may affect their design, development, and performance. Selection and development of optimal microbicide delivery systems (gel/cream, pessary, film, tablet, foam, etc.), their inactive ingredients, manufacturing details, and packaging system are dependent on the properties of active drug, or their preformulation parameters (PP). The PP of the active drug substance needs to be evaluated in initial stages of drug discovery and development so that the most suitable delivery system can be selected. Some PP of microbicide agents include physical state, organoleptic properties (color, odor, appearance, taste, etc.), molecular weight, aqueous solubility, hygroscopicity, acidity/alkalinity, permeability and absorption characteristics, stability in solid/solution state, and inherent bioadhesiveness. Thus, a well-coordinated, planned, and implemented preformulation program can help in not only accelerating microbicide formulation development, but also to minimize unforeseen failures in subsequent stages of the development. The objective of this review is to highlight the significance of PP, suggesting a systematic preformulation program.
Stability of an extemporaneously compounded minoxidil oral suspension
Publisher: Oxford University Press (OUP)
Date: 03-2018
DOI: 10.2146/AJHP160457
Abstract: Results of a study to determine the stability of an extemporaneously compounded minoxidil oral suspension under various temperature and stress conditions are reported. Commercially available minoxidil tablets (10 mg) were crushed to a fine powder, and predetermined amounts of 2 suspending vehicles were added to produce a 1-mg/mL suspension, which was stored in glass bottles at room temperature (25 ± 2 °C) or in a refrigerator (4 ± 2 °C). To simulate daily patient use, 5 days weekly 1 bottle of the suspension was removed from refrigerated storage and shaken and 0.5 mL of the contents discarded. At each specified time point, s les were analyzed in duplicate ( The mean percentage of initial minoxidil concentration remaining in all refrigerated s les exceeded 90% throughout the 24-week study, with no change in appearance, pH, microbial activity, odor, or redispersibility. During storage at room temperature, the suspension exhibited a color change at week 4, with slight sedimentation after 6 weeks, although minoxidil recovery exceeded 90% for 10 weeks. An extemporaneously compounded minoxidil oral suspension was stable for 24 weeks when stored in a refrigerator. This suspension can be used for up to 3 weeks when stored at room temperature.
Multifunctional ultrasmall AgNP hydrogel accelerates healing of S. aureus infected wounds
Publisher: Elsevier BV
Date: 07-2021
Formulation Optimization of Chitosan-Stabilized Silver Nanoparticles Using In Vitro Antimicrobial Assay
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.XPHS.2018.09.011
Abstract: Antimicrobial resistance at the infected site is a serious medical issue that increases patient morbidity and mortality. Silver has antibacterial activity associated with some dose-dependent toxicity. Silver nanoparticles, due to larger surface area, have antibacterial properties, which make them useful in the treatment of infections. Chitosan-stabilized silver nanoparticles (CH-AgNP) were formulated and evaluated for minimal inhibitory concentration and minimal bactericidal concentration testing against Staphylococcus aureus ATCC 29213, S aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922, and 20 methicillin-resistant S aureus isolates. Minimum biofilm eradication concentration study was used to evaluate the biofilm reduction, and in vitro antimicrobial checkerboard assays were performed. The effective optimum ratio of AgNP:chitosan solution was 1:4. Minimal inhibitory concentration and minimal bactericidal concentration ranges of CH-AgNP were 4 to 14 times lower compared to AgNP alone against methicillin-resistant S aureus isolates. Minimum biofilm eradication concentration values of CH-AgNP for ATCC PA-01, P aeruginosa isolate 1, and P aeruginosa isolate 2 were found to be >84.59 μg/mL, 42.29 μg/mL, and 21.15 μg/mL, respectively. Thus, CH-AgNP is a potential formulation for wound treatment and management of infected sites associated with antimicrobial resistance.
Influence of Acidic pH on Wound Healing In Vivo: A Novel Perspective for Wound Treatment
Publisher: MDPI AG
Date: 07-11-2022
Abstract: There has been little understanding of acidification functionality in wound healing, highlighting the need to study the efficacy of wound acidification on wound closure and cellular activity in non-infected wounds. This study is focused on establishing the healing potential of wound acidification in non-infected wounds. Acidic buffers, constituting either phosphoric or citric acid, were employed to modify the physiological pH of non-infected full-thickness excisional murine wounds. Acidification of the wound by acidic buffers was found to be an effective strategy to improve wound healing. A significant improvement in wound healing parameters was observed as early as 2 days post-treatment with acidic buffers compared to controls, with faster rate of epithelialization, wound closure and higher levels of collagen at day 7. pH is shown to play a role in mediating the rate of wound healing, with acidic buffers formulated at pH 4 observed to stimulate faster recovery of wounded tissues than pH 6 buffers. Our study shows the importance of maintaining an acidic wound microenvironment at pH 4, which could be a potential therapeutic strategy for wound management.
Drug-eluting non-vascular stents for localised drug targeting in obstructive gastrointestinal cancers
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.JCONREL.2019.07.001
Abstract: Stents are currently the primary choice for the treatment of both vascular and non-vascular occlusions and/or stenosis. Despite the proven history of clinical safety and efficacy, the benefit of traditional vascular or non-vascular stenting is often limited by in-stent restenosis, resulting in failure of existing stent or reintervention by use of another stent. Coronary drug-eluting stents (DESs) significantly reduce restenosis of vascular stents and have revolutionised the percutaneous coronary intervention (PCI) treatment in coronary stenting patients. Following the similar concept of coronary DESs, non-vascular DESs are being investigated to reduce non-vascular restenosis caused by tumour growth, enhance stenting functions, and increase their effectiveness in the treatment of obstructive gastrointestinal (GI) cancers. This article summarises and updates the outcomes of preclinical and clinical studies on non-vascular DESs for localised management of malignant GI obstructions with emphasis on fabrication techniques and regulatory requirements relevant to development and marketing approval.
A new LC-MS/MS bioanalytical method for atenolol in human plasma and milk
Publisher: Future Science Ltd
Date: 04-2017
Abstract: Aim: A new sensitive LC–MS/MS method for the quantification of atenolol in human plasma and milk has been developed for clinical lactation studies. Methods & results: Atenolol and the internal standard, phenazone, were extracted from biological matrices by protein precipitation. A Phenomenex ® C-18 column and gradient chromatographic conditions were used for separation of the analyte, followed by detection with MS. Stability of s les was confirmed for atenolol in human plasma and milk for up to 3 months. Linearity range of 1–800 ng/ml (r 2 = 0.9995), the precision within 15% CV and the recovery of the analyte (80–100% range) were achieved. Conclusion: A new validated analytical method for atenolol in plasma and milk was developed.
Immunomodulatory effects of neem (Azadirachta indica) oil
Publisher: Elsevier BV
Date: 10-1992
DOI: 10.1016/0192-0561(92)90054-O
Abstract: Immunomodulatory effects of neem oil were studied in mice. The animals were treated intraperitoneally (i.p.) with neem oil control animals received the emulsifying agent with or without peanut oil. Peritoneal lavage, collected on subsequent days, showed a maximum number of leukocytic cells on day 3 following treatment with neem oil peritoneal macrophages exhibited enhanced phagocytic activity and expression of MHC class-II antigens. Neem oil treatment also induced the production of gamma interferon. Spleen cells of neem oil-treated animals showed a significantly higher lymphocyte proliferative response to in vitro challenge with Con A or tetanus toxoid (TT) than that of the controls. Pre-treatment with neem oil, however, did not augment the anti-TT antibody response. The results of this study indicate that neem oil acts as a non-specific immunostimulant and that it selectively activates the cell-mediated immune (CMI) mechanisms to elicit an enhanced response to subsequent mitogenic or antigenic challenge.
Three-dimensional printed 5-fluorouracil eluting polyurethane stents for the treatment of oesophageal cancers
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0BM01355B
Abstract: 3D printing is introduced as rapid and facile approach to prepare personalized drug-eluting stents for the treatment of oesophageal cancers.
Analytical Profile of Moxidectin
Publisher: Elsevier
Date: 2013
Localized In Situ Nanoemulgel Drug Delivery System of Quercetin for Periodontitis: Development and Computational Simulations
Publisher: MDPI AG
Date: 06-06-2018
Ion-exchange resins: carrying drug delivery forward
Publisher: Elsevier BV
Date: 09-2001
DOI: 10.1016/S1359-6446(01)01922-5
Abstract: Ion-exchange resins (IER), or ionic polymer networks, have received considerable attention from pharmaceutical scientists because of their versatile properties as drug-delivery vehicles. In the past few years, IER have been extensively studied in the development of novel drug-delivery systems (DDSs) and other biomedical applications. Some of the DDSs containing IER have been introduced into the market. In this review, the applications of IER in drug delivery research are discussed.
Recent Interventions for Nanotechnology Based Drug Products: Insights into the Regulatory Aspects
Publisher: Bentham Science Publishers Ltd.
Date: 28-03-2019
DOI: 10.2174/1381612825666190117094250
Abstract: Nanotechnology has been one of the most prominent forefront grounds in several traditional research areas of science and technology, and development of medicines at nanoscale can be reflected by the tremendous surge in market interest. Its applications include various research areas of medicine, drug delivery technology, diagnostic devices, tissue engineering and gene therapy. Along with immense advances, this technology comes with major limitations including potential immune reactivity and complex characterization of these products. The lack of a proper regulatory perspective due to infidelities in scientific findings have led to further uncertainties and vagueness of the nanoscale domain, particularly its safety implications. Early development pathways and regulations should be a top-notch priority to help researchers fail faster and more economically. This would facilitate the peaking utility of these materials in medicine without compromising public health and environmental integrity. This review attempts to emphasize the regulatory rationales of key considerations in nanotechnology along with a portray of the present scenario.
Further Characterization of Intrastriatal Lipopolysaccharide Model of Parkinson’s Disease in C57BL/6 Mice
Publisher: MDPI AG
Date: 09-07-2021
DOI: 10.3390/IJMS22147380
Abstract: Parkinson’s disease (PD) is the most common movement disorder, characterized by progressive degeneration of the nigrostriatal pathway, which consists of dopaminergic cell bodies in substantia nigra and their neuronal projections to the striatum. Moreover, PD is associated with an array of non-motor symptoms such as olfactory dysfunction, gastrointestinal dysfunction, impaired regulation of the sleep-wake cycle, anxiety, depression, and cognitive impairment. Inflammation and concomitant oxidative stress are crucial in the pathogenesis of PD. Thus, this study aimed to model PD via intrastriatal injection of the inflammagen lipopolysaccharide (LPS)to investigate if the lesion causes olfactory and motor impairments, inflammation, oxidative stress, and alteration in synaptic proteins in the olfactory bulb, striatum, and colon. Ten µg of LPS was injected unilaterally into the striatum of 27 male C57BL/6 mice, and behavioural assessment was conducted at 4 and 8 weeks post-treatment, followed by tissue collection. Intrastriatal LPS induced motor impairment in C57BL/6 mice at 8 weeks post-treatment evidenced by reduced latency time in the rotarod test. LPS also induced inflammation in the striatum characterized by increased expression of microglial marker Iba-1 and astrocytic marker GFAP, with degeneration of dopaminergic neuronal fibres (reduced tyrosine hydroxylase immunoreactivity), and reduction of synaptic proteins and DJ-1 protein. Additionally, intrastriatal LPS induced inflammation, oxidative stress and alterations in synaptic proteins within the olfactory bulb, although this did not induce a significant impairment in olfactory function. Intrastriatal LPS induced mild inflammatory changes in the distal colon, accompanied by increased protein expression of 3-nitrotyrosine-modified proteins. This model recapitulated the major features of PD such as motor impairment and degeneration of dopaminergic neuronal fibres in the striatum, as well as some pathological changes in the olfactory bulb and colon thus, this model could be suitable for understanding clinical PD and testing neuroprotective strategies.
Synthesis and characterization of a novel inulin hydrogel crosslinked with pyromellitic dianhydride
Publisher: Elsevier BV
Date: 2019
Polycationic Silver Nanoclusters Comprising Nanoreservoirs of Ag+ Ions with High Antimicrobial and Antibiofilm Activity
Publisher: American Chemical Society (ACS)
Date: 22-12-2021
Abstract: Silver-based nano-antibiotics are rapidly developing as promising alternatives to conventional antibiotics. Ideally, to remain potent against a wide range of drug-resistant and anaerobic bacteria, silver-based nano-antibiotics should easily penetrate through the bacterial cell walls and actively release silver ions. In this study, highly monodispersed, ultrasmall (<3 nm), polycationic silver nanoclusters (pAgNCs) are designed and synthesized for the elimination of a range of common Gram-negative and Gram-positive pathogens and their corresponding established and matured biofilms, including those composed of multiple species. The pAgNCs also show greatly enhanced antibacterial efficacy against anaerobic bacteria such as
Application of Exogenous GnRH in Food Animal Production
Publisher: MDPI AG
Date: 06-06-2023
DOI: 10.3390/ANI13121891
Abstract: Over several decades, exogenous GnRH and agonists have been employed for controlling reproductive cascades in animals, and treating some reproductive morbidities. The administration of GnRH is used in animals to counter ovarian dysfunction, induce ovulation, and to increase conception and pregnancy rates. GnRH and its agonists are used in the treatment of cystic ovarian degeneration and repeat breeder syndrome. The development of protocols for GnRH administration by intramuscular injection, intramuscular or subcutaneous implants, and intravaginal deposition has empowered their clinical use worldwide. Currently, exogenous GnRH products are a central part of several pre- and post-breeding programs for the enhancement of fertility, including the control of estrous cycles and timing of ovulation, development of fixed-time artificial insemination protocols, improved embryo survival, and the treatment of reproductive morbidity. The aim of the present review is to summarize the application of exogenous GnRH agonists in food animal production.
In vitro comparison of the dermal penetration of three different topical formulations containing lasalocid
Publisher: Wiley
Date: 03-05-2017
DOI: 10.1111/VDE.12379
Abstract: Topical antimicrobial preparations are of utmost importance in treating suspected and confirmed meticillin-resistant Staphylococcus pseudintermedius (MRSP) infections due to the increasing incidence of widespread resistance to systemic antimicrobials. Lasalocid is active against MRSP in vitro and this may become an important topical antimicrobial for the treatment of canine pyoderma. To determine effects of various formulation types on penetration and retention of lasalocid applied to canine skin in vitro. Normal canine skin was collected from the thorax of five dogs that had been euthanized on the basis of health and/or intractable behavioural issues. Solution, lotion and ointment containing 2% lasalocid were applied to ex vivo canine skin. Transdermal penetration was assessed for a 24 h period and retention of lasalocid was assessed at the conclusion of the study. The solution had significantly higher skin retention of lasalocid and proportion of applied dose retained in skin than lotion and ointment (Tukey-Kramer Honest Significant Difference test, P < 0.01). Lasalocid could not be detected in the receptor fluid of any Franz cell at any time point. Lasalocid was not identified in the receptor fluid of any s le, indicating that systemic absorption of the active ingredient in vivo is unlikely. Lasalocid may be useful in the treatment of MRSP infections if in vivo studies support safety and efficacy.
Compatibility studies between isosorbide mononitrate and selected excipients used in the development of extended release formulations
Publisher: Elsevier BV
Date: 05-2004
Osmotic Pumps in Drug Delivery
Publisher: Begell House
Date: 2004
DOI: 10.1615/CRITREVTHERDRUGCARRIERSYST.V21.I6.20
Abstract: In recent years, novel drug delivery systems (NDDS) have been recognized as an attractive niche for the pharmaceutical and health industry. Among various NDDS, osmotic pumps have matured from their use with laboratory animals to the most reliable controlled release systems for humans. Osmotically controlled drug delivery systems use osmotic pressure for controlled delivery of active agent(s). Drug delivery from these systems, to a large extent, is independent of the physiological factors of the gastrointestinal tract. Because of their unique advantages over other types of dosage forms, osmotic pumps form a class of their own among the various drug delivery technologies, and a variety of products based on this technology are available on the market. This article is a review of different types of osmotic pumps and their role in drug delivery.
A new LC-MS/MS bioanalytical method for perindopril and perindoprilat in human plasma and milk
Publisher: Springer Science and Business Media LLC
Date: 25-08-2017
DOI: 10.1007/S00216-017-0552-Y
Abstract: A first of its kind, simple, rapid, and sensitive liquid chromatography mass spectrometry (LC-MS/MS) method was developed and validated for quantification of perindopril and perindoprilat in both human plasma and breast milk. The analytes and internal standards (phenazone and acetyl salicylic acid) were extracted from biological matrices by protein precipitation. A Phenomenex® C-18 column was used to provide an appropriate chromatographic separation of the analytes, followed by detection with tandem mass spectrometry. Gradient chromatographic and mass spectrometric detection conditions with mobile phases (A: 5% methanol + 0.1% formic acid in water v/v, and B: 95% methanol + 0.1% formic acid in water v/v) were developed to achieve a LOQ of 0.5 ng/mL in both human plasma and milk. The method was suitable of evaluating clinical s les. The mass transition was followed as m/z 369.10/172.00 for perindopril, m/z 339.00/168.10 for perindoprilat, m/z 188.90/55.95 for phenazone, and m/z 179.04/137.02 for acetyl salicylic acid. The developed method was optimized and validated with a linear range of 0.1-200 ng/mL (r
Electrically switchable polypyrrole film for the tunable release of progesterone
Publisher: Future Science Ltd
Date: 03-2013
DOI: 10.4155/TDE.12.166
Abstract: Background: Intrinsically conducting polymers, such as polypyrrole (PPy), have been utilized for drug delivery purposes as drug release rates can be tuned by electrical stimulation. Electrical stimulation can be used to switch the redox state of PPy, subsequently changing the electrostatic charge and volume of the polymer. Most literature to date has focused on the delivery of charged bioactives. This study aimed to prepare a PPy film formulation where the release rate of the uncharged drug progesterone could be electrically tuned. Results & discussion: In this study PPy films loaded with progesterone are described. Drug loading levels were influenced by the concentration of drug during manufacture and polymerization time. The polymer formulation was electrically conductive and electroactive, switchable between oxidized and reduced states. Drug release was influenced by the application of electrical stimulation, the greatest release was observed on application of +0.8 V (to oxidize the polymer). Triggered release was observed in response to a period of electrical stimulation (±0.8 V at 0.5 Hz). Conclusion: This study describes the preparation of a PPy film loaded with the uncharged drug progesterone. The release rate could be tuned with electrical stimulation.
Development of a novel niosomal system for oral delivery of Ginkgo biloba extract
Publisher: Informa UK Limited
Date: 2013
DOI: 10.2147/IJN.S37984
Development of topical delivery systems for flightless neutralizing antibody
Publisher: Elsevier BV
Date: 07-2017
DOI: 10.1016/J.XPHS.2017.03.012
Abstract: Flightless I (Flii) is an actin remodeling protein important for cytoskeletal regulation and cellular processes including migration, proliferation, and adhesion. Previous studies have clearly identified Flii as a novel therapeutical target for improved wound repair and have demonstrated Flii regulation using Flii neutralizing antibodies (FnAb) in different models of wound healing in vivo. Here we describe the development of an optimized topical delivery system that can neutralize Flii activity in the epidermis. Topical delivery of FnAb is an attractive approach as it provides a convenient application, sustained release, localized effect, and reduced dosage. Three successful formulations were developed, and their physical and chemical stability examined. The in vitro release revealed prolonged and sustained release of FnAb in all the tested formulations. Additionally, penetration studies using intact porcine skin showed that FnAb penetrated the epidermis and upper papillary dermis. The penetrated FnAb significantly reduced Flii expression compared to dosed matched IgG controls. This study has successfully developed a topical delivery system for FnAb that could serve as a potential platform for future localized wound treatments.
Effect of plasticizers on drug-in-adhesive patches containing 5-fluorouracil
Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.IJPHARM.2021.121316
Abstract: Topical patches containing 5-fluorouracil (5-FU) are a feasible alternative to overcome the shortcomings of commercial cream for the treatment of non-melanoma skin cancer (NMSC). Plasticizers are a critical component of drug-in-adhesive (DIA) patches as they can significantly affect the mechanical, adhesive and drug release characteristics of the patches. Eudragit® E (EuE) is a methacrylate-based cationic copolymer capable of producing flexible and adhesive films for topical application. In this study, the effect of plasticizers on the mechanical, adhesive and 5-FU release characteristics of EuE-based patches was comprehensively evaluated. While the elongation at break (%) and adhesion of the films were significantly increased with increasing triacetin, dibutyl sebacate (DBS) and triethyl citrate (TEC) concentrations, the tensile strength showed an inverse relationship. EuE plasticized with 40% triacetin, 30% DBS or 40% w/w TEC produced elastic and adhesive films most suitable for topical application. In vitro release studies of the 5-FU-loaded patches demonstrated an initial burst release pattern during the first 10 min followed by a slow release over 120 min. In summary, this study provides important information on effect of plasticizers for preparation of EuE-based patches with desired mechanical, adhesive and release characteristics of 5-FU towards their potential application in the treatment of NMSC.
Penicillin stability in prefilled syringes for the purpose of skin testing for drug allergy
Publisher: Elsevier BV
Date: 07-2015
LC-DAD Determination of Fleroxacin in Bulk and Pharmaceutical Dosage Forms
Publisher: Springer Science and Business Media LLC
Date: 28-03-2009
Oral administration of a 2-aminopyrimidine robenidine analogue (NCL1 95) significantly reduces Staphylococcus aureus infection and reduces Escherichia coli infection in combination with sub -inhibitory colistin concentrations in a bioluminescent mouse model
Publisher: American Society for Microbiology
Date: 18-10-2023
DOI: 10.1128/AAC.00424-23
Using GPCRs as Molecular Beacons to Target Ovarian Cancer with Nanomedicines
Publisher: MDPI AG
Date: 10-05-2022
Abstract: The five-year survival rate for women with ovarian cancer is very poor despite radical cytoreductive surgery and chemotherapy. Although most patients initially respond to platinum-based chemotherapy, the majority experience recurrence and ultimately develop chemoresistance, resulting in fatal outcomes. The current administration of cytotoxic compounds is h ered by dose-limiting severe adverse effects. There is an unmet clinical need for targeted drug delivery systems that transport chemotherapeutics selectively to tumor cells while minimizing off-target toxicity. G protein-coupled receptors (GPCRs) are the largest family of membrane receptors, and many are overexpressed in solid tumors, including ovarian cancer. This review summarizes the progress in engineered nanoparticle research for drug delivery for ovarian cancer and discusses the potential use of GPCRs as molecular entry points to deliver anti-cancer compounds into ovarian cancer cells. A newly emerging treatment paradigm could be the personalized design of nanomedicines on a case-by-case basis.
Development and In Vitro Evaluation of 5-Fluorouracil-Eluting Stents for the Treatment of Colorectal Cancer and Cancer-Related Obstruction
Publisher: MDPI AG
Date: 24-12-2020
DOI: 10.3390/PHARMACEUTICS13010017
Abstract: Self-expanding metal stents (SEMSs) are currently the gold standard for the localised management of malignant gastrointestinal (GI) stenosis and/or obstructions. Despite encouraging clinical success, in-stent restenosis caused by tumour growth is a significant challenge. Incorporating chemotherapeutic drugs into GI stents is an emerging strategy to provide localised and sustained release of drugs to intestinal malignant tissues to prevent tumour growth. Therefore, the aim of this work was to develop and evaluate a local GI stent-based delivery system that provides a controlled release of 5-fluorouracil (5FU) over a course of several weeks to months, for the treatment of colorectal cancer and cancer-related stenosis/obstructions. The 5FU-loaded GI stents were fabricated via sequential dip-coating of commercial GI stents with a drug-loaded polyurethane (PU) basecoat and a drug-free poly(ethylene-co-vinyl acetate) (PEVA) topcoat. For comparison, two types of commercial stents were investigated, including bare and silicone (Si) membrane-covered stents. The physicochemical properties of the 5FU-loaded stents were evaluated using photoacoustic Fourier-transform infrared (PA-FTIR) spectroscopy, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and thermal analysis. In vitro release studies in biological medium revealed that the 5FU-loaded stents provided a sustained release of drug over the period studied (18 d), and cell viability, cell cycle distribution and apoptosis assays showed that the released 5FU had comparable anticancer activity against human colon cancer cells (HCT-116) to pure 5FU. This study demonstrates that dip-coating is a facile and reliable approach for fabricating drug-eluting stents (DESs) that are promising candidates for the treatment of GI obstructions and/or restenosis.
Evaluation of physical properties and performance over time of an actuating polypyrrole based drug delivery system
Publisher: Elsevier BV
Date: 11-2010
Pure drug and polymer based nanotechnologies for the improved solubility, stability, bioavailability and targeting of anti-HIV drugs
Publisher: Elsevier BV
Date: 03-2010
DOI: 10.1016/J.ADDR.2009.11.019
Abstract: The impact of human immunodeficiency virus (HIV) infection has been devastating with nearly 7400 new infections every day. Although, the advent of highly active antiretroviral therapy (HAART) has made a tremendous contribution in reducing the morbidity and mortality in developed countries, the situation in developing countries is still grim with millions of people being infected by this disease. The new advancements in the field of nanotechnology based drug delivery systems hold promise to improve the situation. These nanoscale systems have been successfully employed in other diseases such as cancer, and therefore, we now have a better understanding of the practicalities and technicalities associated with their clinical development. Nanotechnology based approaches offer some unique opportunities specifically for the improvement of water solubility, stability, bioavailability and targeting of antiretroviral drugs. This review presents discussion on the contribution of pure drug and polymer based nanotechnologies for the delivery anti-HIV drugs.
A Validated Stability-Indicating LC Method for Orbifloxacin in the Presence of Degradation Products
Publisher: Bentham Science Publishers Ltd.
Date: 08-2011
Impact of a Novel Anticoccidial Analogue on Systemic Staphylococcus aureus Infection in a Bioluminescent Mouse Model
Publisher: MDPI AG
Date: 06-01-2022
DOI: 10.3390/ANTIBIOTICS11010065
Abstract: In this study, we investigated the potential of an analogue of robenidine (NCL179) to expand its chemical ersity for the treatment of multidrug-resistant (MDR) bacterial infections. We show that NCL179 exhibits potent bactericidal activity, returning minimum inhibitory concentration/minimum bactericidal concentrations (MICs/MBCs) of 1–2 µg/mL against methicillin-resistant Staphylococcus aureus, MICs/MBCs of 1–2 µg/mL against methicillin-resistant S. pseudintermedius and MICs/MBCs of 2–4 µg/mL against vancomycin-resistant enterococci. NCL179 showed synergistic activity against clinical isolates and reference strains of Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa in the presence of sub-inhibitory concentrations of colistin, whereas NCL179 alone had no activity. Mice given oral NCL179 at 10 mg/kg and 50 mg/kg (4 × doses, 4 h apart) showed no adverse clinical effects and no observable histological effects in any of the organs examined. In a bioluminescent S. aureus sepsis challenge model, mice that received four oral doses of NCL179 at 50 mg/kg at 4 h intervals exhibited significantly reduced bacterial loads, longer survival times and higher overall survival rates than the vehicle-only treated mice. These results support NCL179 as a valid candidate for further development to treat MDR bacterial infections as a stand-alone antibiotic or in combination with existing antibiotic classes.
Related Organisations
National Institute Of Pharmaceutical Education And Research
Location: India
Related Funding Activities
Linkage Projects - Grant ID: LP140100142
Start Date: 05-2015
End Date: 06-2019
Amount: $330,000.00
Funder: Australian Research Council
View Funded ActivityLinkage Projects - Grant ID: LP210301109
Start Date: 12-2023
End Date: 12-2026
Amount: $282,339.00
Funder: Australian Research Council
View Funded ActivityLinkage Infrastructure, Equipment And Facilities - Grant ID: LE170100093
Start Date: 2017
End Date: 07-2018
Amount: $510,000.00
Funder: Australian Research Council
View Funded Activity