ORCID Profile
0000-0001-7372-1456
Current Organisation
University of Parma
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Publisher: AME Publishing Company
Date: 2018
Publisher: MDPI AG
Date: 30-09-2018
DOI: 10.20944/PREPRINTS201809.0595.V1
Abstract: Lipid-based drugs are emerging as an interesting class of novel anticancer drugs with the potential to target specific cancer cell metabolic pathway linked to their proliferation and invasiveness. In particular, & omega & minus polyunsaturated fatty acids (PUFA) derivatives such as epoxides and their bioisosteres have demonstrated the potential to suppress growth and promote apoptosis in triple-negative human breast cancer cells MDA-MB-231. In this study 16-(4& rsquo -chloro-3& rsquo -trifluorophenyl)carbamoylamino]hexadecanoic acid (ClFPh-CHA), an anticancer lipid derived from & omega & minus ,17,18-epoxyeicosanoic acid, was formulated as a stable nanoemulsion with size around 150 nm and narrow droplet size distribution (PDI& .200) through phase-inversion emulsification process followed by high pressure homogenization in view of an oral administration. The ClFPh-CHA-loaded nanoemulsions were able to significantly decrease the relative tumor volume in mice bearing an intramammary tumor xenograft at all doses tested (2.5, 10 and 40 mg/kg) after 32 days of daily oral administration. Furthermore, absolute tumor weight was decreased to 50% of untreated control at 10 and 40 mg/kg, while intraperitoneal administration could achieve a significant reduction only at the highest dose of 40 mg/kg. Results suggest that oral administration of ClFPh-CHA formulated as a nanoemulsion has a sufficient bioavailability to provide an anticancer effect in mice and that the activity is at least equal if not superior to that obtained by a conventional parenteral administration of equivalent doses of the same drug.
Publisher: Elsevier BV
Date: 02-2016
DOI: 10.1016/J.EJPS.2016.01.002
Abstract: Lecithin and hyaluronic acid were used for the preparation of polysaccharide decorated nanoparticles loaded with vitamin E using the cationic lipid dioctadecyldimethylammonium bromide (DODMA). Nanoparticles showed mean particle size in the range 130-350 nm and narrow size distribution. Vitamin E encapsulation efficiency was higher than 99%. These nanoparticles were incorporated in polymeric films containing Aloe vera extract, hyaluronic acid, sodium alginate, polyethyleneoxide (PEO) and polyvinylalcohol (PVA) as an innovative treatment in skin wounds. Films were thin, flexible, resistant and suitable for application on burn wounds. Additionally, in vitro occlusion study highlighted the dependence of the occlusive effect on the presence of nanoparticles. The results obtained show that the bioadhesive films containing vitamin E acetate and Aloe vera could be an innovative therapeutic system for the treatment of skin wounds, such as burns. The controlled release of the vitamin along with a reduction in water loss through damaged skin provided by the nanoparticle-loaded polymer film are considered important features for an improvement in wound healing and skin regeneration.
Publisher: American Chemical Society (ACS)
Date: 14-07-2021
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.EJPS.2018.07.035
Abstract: Malignant pleural mesothelioma (MPM) is a rare malignancy characterized by a long latency period of 20-50 years after exposure to the main aetiology agent that is asbestos. MPM treatments include surgery, chemotherapy, and radiation therapy, with the combination pemetrexed and cisplatin being the standard chemotherapy approach. Despite this multimodality therapy one of the major issues after surgery is the high rate of local recurrence of the tumor. One possible approach would be the intrapleural application of implants loaded with anticancer drug to be applied during surgery to prevent local tumor recurrence. The implant proposed in the present work is a polymeric film of hyaluronic acid loaded with pemetrexed. The film developed is a hydrophilic, thin and flexible film sufficiently resistant to be applied intrapleurally adhering to the mesothelial surface. The release of pemetrexed from the film was found to be complete within2 h in phosphate buffered saline. In an orthotopic model of mesothelioma recurrence in rats, pemetrexed loaded films showed the same antitumor efficacy of pemetrexed disodium solutions administered intravenously or intrapleurally, while when administered in combination with cisplatin-loaded hyaluronate film, the implants almost completely prevented tumor recurrence. The local administration of drug-loaded polymer implants appears an ideal chemotherapy strategy especially for patients in which surgery is already selected as a viable therapeutic option.
Publisher: MDPI AG
Date: 09-03-2021
DOI: 10.3390/PHARMACEUTICS13030362
Abstract: Pleural mesothelioma is a lung diffuse tumor, whose complete resection is unlikely. Consequently, metastases reappear where the primary tumor was removed. This paper illustrates the orphan medicine designation procedure of an intracavitary cisplatin film and related pharmaceutical development aspects requested by the European Medicines Agency (EMA) in its Scientific Advice. Since cisplatin pharmacokinetics from the implanted film in sheep resulted substantially modified compared to intravenous administration, the formation of a cisplatin/hyaluronan complex had been hypothesized. Here, the interaction between sodium hyaluronate (NaHA) and cisplatin (CisPt) was demonstrated. Size exclusion chromatography qualitatively evidenced the complex in the film-forming mixture, only showing the NaHA peak. Atomic absorption spectroscopy of the corresponding fraction revealed platinum, confirming the interaction. Reverse phase HPLC quantified about 5% free cisplatin in the film-forming mixture, indirectly meaning that 95% was complexed. Finally, a study of CisPt release from the film assessed how CisPt/NaHA complex affected drug availability. In water, a medium without chloride ions, there was no release and the film remained intact for 48 h and longer, whereas the placebo film dissolved in 15 min. In 0.9% NaCl medium, the film became more soluble, dissolving within 3–4 h. However, cisplatin release was still controlled by the existing complex in solution until chloride ions displaced it. While the film modified its dissolution with aging, CisPt release remained unaffected (90% released in 48 h).
Publisher: Elsevier BV
Date: 09-2005
DOI: 10.1016/J.IJPHARM.2005.05.041
Abstract: In this paper, compendial sodium alginate beads have been manufactured by laminar jet break-up technology. The effect of polymer concentration, viscosity and polymeric solution flow rate on the characteristics of beads was studied. Size distribution of alginate beads in the hydrated state was strongly dependent on the flow rate and viscosity of polymer solutions, since a transition from laminar jet break-up conditions to vibration-assisted dripping was observed. The re-hydration kinetics of dried beads in simulated gastric fluid (SGF) showed that the maximum swelling of beads was reached after 1-2 h, with an increase in volume of two to three times and a time lag dependent on the polymer concentration. The re-hydration swelling profiles in simulated intestinal fluid (SIF) showed no time lag and higher swelling volume moreover, in this medium after the maximum swelling was reached, the bead structure was quickly disaggregated because of the presence in the medium of phosphate able to capture calcium ions present in the alginate gel structure.
Publisher: Wiley
Date: 31-05-2011
DOI: 10.1002/JBM.A.33123
Abstract: Microencapsulation of cells is a promising approach to prevent rejection in the absence of immunosuppression. Clinical application, however, is h ered by insufficient insight in factors influencing biocompatibility of the capsules in humans. In the present study we exposed alginate-based capsules prepared of different types of alginate to human peritoneal fluid. Subsequently we studied the physicochemical changes of the capsule's surface by applying micro-Fourier Transform Infrared Spectroscopy. We did test alginate-beads and alginate-poly-L-lysine capsules prepared of different types of alginate. In all tested capsule formulations we found adsorption of components from human peritoneal fluid and clear physicochemical changes of the surface. These changes were alginate-dependent. The adsorption had no significant effects on the permselective properties of the capsule but we found a strong increase of TNFα production by human peripheral blood mononuclear cells when exposed to alginate-beads treated with human peritoneal fluid. This elevated responsiveness was not observed with alginate-PLL capsules. The results show that alginate-based capsule surfaces always undergo physicochemical changes of the surface when exposed to human peritoneal fluid. This adsorption may lead to enhancement of the inflammatory responses against the microcapsules. Our result implicate that biocompatibility measurements should not only been done with freshly prepared capsules but also with capsules that have been exposed to fluid from the implantation site in order to predict the in vivo responses.
Publisher: MDPI AG
Date: 09-06-2021
DOI: 10.3390/PHARMACEUTICS13060855
Abstract: There is increasing consensus in considering statins beneficial for age-related macular degeneration and in general, for immune and inflammatory mediated diseases affecting the posterior segment of the eye. However, all available data relate to oral administration, and safety and effectiveness of statins directly administered to the eye are not yet known, despite their ophthalmic administration could be beneficial. The aim was the development and the characterization of polymeric micelles based on TPGS or TPGS oloxamer 407 to increase simvastatin solubility and stability and to enhance the delivery of the drug to the posterior segment of the eye via trans-scleral permeation. Simvastatin was chosen as a model statin and its active hydroxy acid metabolite was investigated as well. Results demonstrated that polymeric micelles increased simvastatin solubility at least 30-fold and particularly TPGS oloxamer 407 mixed micelles, successfully stabilized simvastatin over time, preventing the hydrolysis when stored for 1 month at 4 °C. Furthermore, both TPGS (1.3 mPas) and mixed micelles (33.2 mPas) showed low viscosity, suitable for periocular administration. TPGS micelles resulted the best performing in delivery simvastatin either across conjunctiva or sclera in ex vivo porcine models. The data pave the way for a future viable ocular administration of statins.
Publisher: Elsevier BV
Date: 04-2008
Publisher: Elsevier BV
Date: 28-02-2011
DOI: 10.1016/J.IJPHARM.2010.11.050
Abstract: The aim of this research was to design and study norfloxacin (NFX) release in floating conditions from compressed hydrophilic matrices of hydroxypropylmethylcellulose (HPMC) or poly(ethylene oxide) (PEO). Module assembling technology for drug delivery system manufacturing was used. Two differently cylindrical base curved matrix/modules, identified as female and male, were assembled in void configuration by friction interlocking their concave bases obtaining a floating release system. Drug release and floatation behavior of this assembly was investigated. Due to the higher surface area exposed to the release medium, faster release was observed for in idual modules compared to their assembled configuration, independently on the polymer used and concentration. The release curves analyzed using the Korsmeyer exponential equation and Peppas & Sahlin binomial equation showed that the drug release was controlled both by drug diffusion and polymer relaxation or erosion mechanisms. However, convective transport was predominant with PEO and at low content of polymers. NFX release from PEO polymeric matrix was more erosion dependent than HPMC. The assembled systems were able to float in vitro for up to 240min, indicating that this drug delivery system of norfloxacin could provide gastro-retentive site-specific release for increasing norfloxacin bioavailability.
Publisher: American Chemical Society (ACS)
Date: 09-2017
DOI: 10.1021/ACS.MOLPHARMACEUT.7B00348
Abstract: The aim of this work was to develop an innovative microemulsion with gel-like properties for the cutaneous delivery of imiquimod, an immunostimulant drug employed for the treatment of cutaneous infections and neoplastic conditions. A pseudoternary phase diagram was built using a 1/1 TPGS (d-α-tocopheryl polyethylene glycol 1000 succinate)/Transcutol mixture as surfactant system, and oleic acid as oil phase. Eight microemulsions-selected from the 1.25/8.75 oil/surfactants ratio, along the water dilution line (from 20 to 56% w/w)-were characterized in terms of rheological behavior, optical properties via polarized microscopy, and supramolecular structure using X-ray scattering. Then, these formulations were loaded with imiquimod and the uptake and distribution into the skin was evaluated on full-thickness porcine skin. X-ray scattering experiments revealed the presence of disconnected drops in the case of microemulsion with 20% water content. Diluting the system up to 48% water content, the structure turned into an interconnected lamellar microemulsion, reaching a proper disconnected lamellar structure for the highest water percentages (52-56%). Upon water addition, also the rheological properties changed from nearly Newtonian fluids to gel-like structures, displaying the maximum of viscosity for the 48% water content. Skin uptake experiments demonstrated that formulation viscosity, drug loading, and surfactant concentration did not play an important role on imiquimod uptake into the skin, while the skin penetration was related instead to the microemulsion mesostructure. In fact, drug uptake became enhanced by locally lamellar interconnected structures, while it was reduced in the presence of disconnected structures, either drops or proper lamellae. Finally, the data demonstrated that mesostructure also affects the drug distribution between the epidermis and dermis. In particular, a significantly higher dermal accumulation was found when disconnected lamellar structures are present, suggesting the possibility of tuning both drug delivery and localization into the skin by modifying microemulsions composition.
Publisher: Springer Science and Business Media LLC
Date: 03-2006
DOI: 10.1208/PT070109
Abstract: The aim of this work was to study the acid neutralization characteristics of microwave-dried sucralfate gel in relation to the water content and physical structure of the substance. Several dried sucralfate gels were compared with humid sucralfate gel and sucralfate nongel powder in terms of neutralization rate and buffering capacity. Humid sucralfate gel and microwave-dried gel exhibited antacid effectiveness. In particular, the neutralization rate of dried gel powders was inversely related to the water content: as the water content of dried powders decreased, the acid reaction rate linearly increased. The relationship was due to the different morphology of dried sucralfate gels. In fact, the porosity of the dried s les increased with the water reduction. However, the acid neutralization equivalent revealed that the dried sucralfate gel became more resistant to acid attack in the case of water content below 42%. Then, the microwave drying procedure had the opposite effect on the reactivity of the aluminum hydroxide component of dried sucralfate gel powders, since the rate of the reaction increased whereas the buffering capacity decreased as the amount of water was reduced.
Publisher: Springer Science and Business Media LLC
Date: 22-07-2015
Publisher: Elsevier BV
Date: 10-2022
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.IJPHARM.2015.06.021
Abstract: Tamoxifen citrate is an anticancer drug slightly soluble in water. Administered orally, it shows great intra- and inter-patient variations in bioavailability. We developed a nanoformulation based on phospholipid and chitosan able to efficiently load tamoxifen and showing an enzyme triggered release. In this work the permeation of tamoxifen released from lecithin/chitosan nanoparticles across excised rat intestinal wall mounted in an Ussing chamber was investigated. Compared to tamoxifen citrate suspension, the amount of the drug permeated using the nanoformulation was increased from 1.5 to 90 times, in absence or in presence of pancreatin or lipase, respectively. It was also evidenced the formation of an active metabolite of tamoxifen, 4-hydroxy tamoxifen, however, the amount of metabolite permeated remained roughly constant in all experiments. The effect of enzymes on intestinal permeation of tamoxifen was shown only when tamoxifen-loaded nanoparticles were in intimate contact with the mucosal surface. The encapsulation of tamoxifen in lecithin/chitosan nanoparticles improved the non-metabolized drug passing through the rat intestinal tissue via paracellular transport.
Publisher: MDPI AG
Date: 26-10-2020
DOI: 10.3390/NANO10112123
Abstract: Polyhydroxyalkanoate (PHA) copolymers show a relatively higher in vivo degradation rate compared to other PHAs, thus, they receive a great deal of attention for a wide range of medical applications. Nanoparticles (NPs) loaded with poorly water-soluble anticancer drug docetaxel (DCX) were produced using poly(3-hydroxybutyrate-co-4-hydroxybutyrate), P(3HB-co-4HB), copolymers biosynthesised from Cupriavidus malaysiensis USMAA1020 isolated from the Malaysian environment. Three copolymers with different molar proportions of 4-hydroxybutirate (4HB) were used: 16% (PHB16), 30% (PHB30) and 70% (PHB70) 4HB-containing P(3HB-co-4HB). Blank and DCX-loaded nanoparticles were then characterized for their size and size distribution, surface charge, encapsulation efficiency and drug release. Preformulation studies showed that an optimised formulation could be achieved through the emulsification/solvent evaporation method using PHB70 with the addition of 1.0% PVA, as stabilizer and 0.03% VitE-TPGS, as surfactant. DCX-loaded PHB70 nanoparticles (DCX-PHB70) gave the desired particle size distribution in terms of average particle size around 150 nm and narrow particle size distribution (polydispersity index (PDI) below 0.100). The encapsulation efficiency result showed that at 30% w/w drug-to-polymer ratio: DCX- PHB16 NPs were able to encapsulate up to 42% of DCX DCX-PHB30 NPs encapsulated up to 46% of DCX and DCX-PHB70 NPs encapsulated up to 50% of DCX within the nanoparticle system. Approximately 60% of DCX was released from the DCX-PHB70 NPs within 7 days for 5%, 10% and 20% of drug-to-polymer ratio while for the 30% and 40% drug-to-polymer ratios, an almost complete drug release (98%) after 7 days of incubation was observed.
Publisher: Bentham Science Publishers Ltd.
Date: 06-2022
DOI: 10.2174/2667387816666220420124648
Abstract: Vaccines are one of the greatest medical achievements of modern medicine. The nasal mucosa represents an effective route of vaccination for both mucosal immunity and peripheral, being at the same time an inductive and effector site of immunity. In this paper, the innovative and patented compositions and manufacturing procedures of nanomaterials have been studied using the peerreviewed research literature. Nanomaterials have several properties that make them unique as adjuvant for vaccines. Nanoadjuvants through the influence of antigen availability over time affect the immune response. Namely, the amount of antigen reaching the immune system or its release over prolonged periods of time can be effectively increased by nanoadjuvants. Mucosal vaccines are an interesting alternative for immunization of diseases in which pathogens access the body through these epithelia. Nanometric adjuvants are not only a viable approach to improve the efficacy of nasal vaccines but in most of the cases they represent the core of the intellectual property related to the innovative vaccine.
Publisher: Springer Science and Business Media LLC
Date: 21-04-2009
Publisher: MDPI AG
Date: 09-02-2018
DOI: 10.20944/PREPRINTS201802.0077.V1
Abstract: In the field of nasal delivery, one of the most fascinating applications is the delivery of drugs directly to the central nervous system bypassing the blood brain barrier. This approach would provide a series of benefits, such as dose lowering and direct targeting of potent drugs, ultimately reducing their systemic side effects. Recently, clinical trials have explored the nasal administration of insulin for the treatment of Alzheimer& rsquo s disease, with promising results. The use of nanomedicines could provide further options for making nose-to-brain delivery reality. In particular, apart from the selection of devices able to deposit the formulation in the upper part of the nose, surface modification of these nanomedicines appears the key strategy to optimize the delivery of drugs from the nasal cavity to the brain. In this review, nanomedicines delivery approaches based on surface electrostatic charges, mucoadhesive polymers, as well as chemical moieties targeting nasal epithelium, will be discussed and critically evaluated for nose-to-brain delivery.
Publisher: Elsevier BV
Date: 04-2016
DOI: 10.1016/J.IJPHARM.2016.02.005
Abstract: In this work different nebulisers were investigated in order to assess their efficiency in combination with colistimethate sodium (CMS) inhalation products. Four nebulisers, namely I-neb(®), Aeroneb(®) Go, eFlow(®)rapid and PARI LC(®) Sprint were studied in terms of delivered dose (DD), drug delivery rate (DDR) and respirable dose (RD) of CMS. The goal was to provide scientific data to physicians for prescribing the most appropriate nebuliser for the CMS specific user. All the apparatuses nebulised ColiFin 1MIU/3 ml solution (80 mg of CMS) with delivered doses between 31% and 41% of the loaded amount. Aeroneb Go showed the longest nebulisation time (more than 20 min). When ColiFin 2 MIU/4 ml was nebulised with eFlow rapid or PARI LC Sprint, the CMS respirable dose was 45.3mg and 39.2mg, in times of 5.6 and 10.8 min, respectively. I-neb, having a medication cup capacity limited to 0.4 ml, loaded with Promixin 0.4 MIU/0.4 ml (32 mg of CMS), provided in a time of 9 min a RD of 21.5mg, a value slightly higher than those obtained by nebulising ColiFin 1 MIU/3 ml with the other nebulisers (range 15.9-17.6 mg). The results illustrate that the clinical outcome depends on the comparative analysis of nebulisation efficiency (respirable dose) and convenience (time), not disregarding the ratios between the amount loaded, delivered and deposited at lung level.
Publisher: Elsevier BV
Date: 2007
Publisher: Royal Society of Chemistry (RSC)
Date: 2010
DOI: 10.1039/B916139B
Publisher: MDPI AG
Date: 17-06-2019
DOI: 10.3390/PHARMACEUTICS11060284
Abstract: Ucuùba fat is fat obtained from a plant found in South America, mainly in Amazonian Brazil. Due to its biocompatibility and bioactivity, Ucuùba fat was used for the production of ketoconazole-loaded nanostructured lipid carriers (NLC) in view of an application for the treatment of onychomycosis and other persistent fungal infections. The development and optimization of Ucuùba fat-based NLC were performed using a Box-Behnken design of experiments. The independent variables were surfactant concentration (% w/v), liquid lipids concentration (% w/v), solid lipids concentration (% w/v), while the outputs of interest were particle size, polydispersity index (PDI) and drug encapsulation efficiency (EE). Ucuùba fat-based NLC were produced and the process was optimized by the development of a predictive mathematical model. Applying the model, two formulations with pre-determined particle size, i.e., 30 and 85 nm, were produced for further evaluation. The optimized formulations were characterized and showed particle size in agreement to the predicted value, i.e., 33.6 nm and 74.6 nm, respectively. The optimized formulations were also characterized using multiple techniques in order to investigate the solid state of drug and excipients (DSC and XRD), particle morphology (TEM), drug release and interactions between the formulation components (FTIR). Furthermore, particle size, surface charge and drug loading efficiency of the formulations were studied during a one-month stability study and did not show evidence of significant modification.
Publisher: Elsevier
Date: 2007
Publisher: MDPI AG
Date: 25-03-2022
DOI: 10.3390/NANO12071073
Abstract: Curcumin (CUR) and quercetin (QU) are potential compounds for treatment of brain diseases such as neurodegenerative diseases (ND) because of their anti-inflammatory and antioxidant properties. However, low water solubility and poor bioavailability hinder their clinical use. In this context, nanotechnology arises as a strategy to overcome biopharmaceutical issues. In this work, we develop, characterize, compare, and optimize three different omega-3 (ω-3) fatty acids nanoemulsions (NEs) loaded with CUR and QU (negative, cationic, gelling) prepared by two different methods for administration by intranasal route (IN). The results showed that formulations prepared with the two proposed methods exhibited good stability and were able to incorporate a similar amount of CUR and QU. On the other side, differences in size, zeta potential, in vitro release kinetics, and permeation/retention test were observed. Considering the two preparation methods tested, high-pressure homogenization (HPH) shows advantages, and the CQ NE- obtained demonstrated potential for sustained release. Toxicity studies demonstrated that the formulations were not toxic for
Publisher: Informa UK Limited
Date: 12-2016
DOI: 10.2147/IJN.S119033
Publisher: Elsevier BV
Date: 06-2018
DOI: 10.1016/J.JPBA.2018.03.046
Abstract: Hybrid nanocapsules constituted of phospholipids and polysaccharides have been proposed as colloidal systems for the delivery of drugs via non-parenteral administration routes, due their capacity of high drug loading, controlled drug release and targeted delivery to the specific organ. Moreover, nanoparticles systems offer the possibility of co-encapsulation of drugs in the same drug delivery system and, consequently, the simultaneous administration of compounds. Characterization of nanoparticles properties, specifically involves quantification of the active pharmaceutical ingredients and is pivotal in the development of innovative nanomedicines. Therefore, this study has proposed and validated a new RP-HPLC-UV method for the simultaneous determination of simvastatin and coenzyme Q10 in hybrid nanoparticles systems. A reversed phase (RP) C8 column and a gradient elution of water: methanol at flow rate of 1.5 ml/min was used. Simvastatin (SVT), simvastatin hydroxyacid isoform (SVA) and coenzyme Q10 were identified by dual wavelength-UV detection at 238 nm (statins) and 275 nm, respectively. The proposed method was selective and linear in the range of 0.5-25 μg/ml (r
Publisher: Elsevier BV
Date: 2010
Publisher: Physical Society of Japan
Date: 2013
Publisher: Informa UK Limited
Date: 11-02-2019
Publisher: MDPI AG
Date: 23-09-2021
DOI: 10.3390/PHARMACEUTICS13101541
Abstract: To overcome some of the shortfalls of the types of dissolution testing currently used for pulmonary products, a new custom-built dissolution apparatus has been developed. For inhalation products, the main in vitro characterisation required by pharmacopoeias is the deposition of the active pharmaceutical ingredient in an impactor to estimate the dose delivered to the target site, i.e., the lung. Hence, the collection of the respirable dose ( µm) also appears to be an essential requirement for the study of the dissolution rate of particles, because it results as being a relevant parameter for the pharmacological action of the powder. In this sense, dissolution studies could become a complementary test to the routine testing of inhaled formulation delivered dose and aerodynamic performance, providing a set of data significant for product quality, efficacy and/or equivalence. In order to achieve the above-mentioned objectives, an innovative dissolution apparatus (RespiCell™) suitable for the dissolution of the respirable fraction of API deposited on the filter of a fast screening impactor (FSI) (but also of the entire formulation if desirable) was designed at the University of Parma and tested. The purpose of the present work was to use the RespiCell dissolution apparatus to compare and discriminate the dissolution behaviour after aerosolisation of various APIs characterised by different physico-chemical properties (hydrophilic/lipophilic) and formulation strategies (excipients, mixing technology).
Publisher: Elsevier BV
Date: 10-2023
Publisher: Springer Science and Business Media LLC
Date: 03-09-2021
DOI: 10.1007/S13311-021-01109-3
Abstract: Polymeric nanoparticles are being extensively investigated as an approach for brain delivery of drugs, especially for their controlled release and targeting capacity. Nose-to-brain administration of nanoparticles, bypassing the blood brain barrier, offers a promising strategy to deliver drugs to the central nervous system. Here, we investigated the potential of hybrid nanoparticles as a therapeutic approach for demyelinating diseases, more specifically for Krabbe’s disease. This rare leukodystrophy is characterized by the lack of enzyme galactosylceramidase, leading to the accumulation of toxic psychosine in glial cells causing neuroinflammation, extensive demyelination and death. We present evidence that lecithin/chitosan nanoparticles prevent damage associated with psychosine by sequestering the neurotoxic sphingolipid via physicochemical hydrophobic interactions. We showed how nanoparticles prevented the cytotoxicity caused by psychosine in cultured human astrocytes in vitro, and how the nanoparticle size and PDI augmented while the electrostatic charges of the surface decreased, suggesting a direct interaction between psychosine and the nanoparticles. Moreover, we studied the effects of nanoparticles ex vivo using mouse cerebellar organotypic cultures, observing that nanoparticles prevented the demyelination and axonal damage caused by psychosine, as well as a moderate prevention of the astrocytic death. Taken together, these results suggest that lecithin-chitosan nanoparticles are a potential novel delivery system for drugs for certain demyelinating conditions such as Krabbe’s disease, due to their dual effect: not only are they an efficient platform for drug delivery, but they exert a protective effect themselves in t ering the levels of psychosine accumulation.
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.EJPS.2017.10.024
Abstract: Coenzyme Q
Publisher: Informa UK Limited
Date: 19-05-2019
Publisher: MDPI AG
Date: 27-10-2019
DOI: 10.20944/PREPRINTS201910.0296.V1
Abstract: Glioblastoma (GBM) is the most lethal form of brain tumor, characterized by rapid growth and surrounding tissue invasion. The current standard treatment is surgery followed by radiotherapy, and concurrent chemotherapy, typically with temozolomide. Although extensive research has been performed over the past years to develop an effective therapeutic strategy for the treatment of GBM, efforts have not provided major improvements in the overall survival of patients with GBM. Thus, new therapeutic approaches are urgently needed. A major challenge in the development of therapies for central nervous system (CNS) disorders is overcoming the blood& ndash brain barrier (BBB). In this context, the intranasal (IN) route of drug administration has been proposed as a non-invasive alternative route to directly targeting the CNS. In fact, this route of drug administration may bypass the blood-brain barrier and reduce systemic side effects. Recently, formulations have been developed to further enhance nose-to-brain transport, mainly with the use of nano-sized and nanostructured drug delivery systems. The focus of this review will be on the strategies developed to deliver a number of anticancer compounds for the treatment of GBM using the nasal administration. In particular, the specific properties of nanomedicines proposed for the nose-to-brain delivery will be critically evaluated. The number of preclinical and clinical data reviewed support the idea that nasal delivery of anticancer drugs might represent a breakthrough advancement in the fight against GBM.
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.EJPS.2017.09.027
Abstract: In the field of nasal drug delivery, among the preparations defined by the European Pharmacopoeia, nasal powders facilitate the formulation of poorly water-soluble active compounds. They often display a simple composition in excipients (if any), allow for the administration of larger drug doses and enhance drug diffusion and absorption across the mucosa, improving bioavailability compared to nasal liquids. Despite the positive features, however, nasal products in this form still struggle to enter the market: the few available on the market are Onzetra Xsail® (sumatriptan) for migraine relief and, for the treatment of rhinitis, Rhinocort® Turbuhaler® (budesonide), Teijin Rhinocort® (beclomethasone dipropionate) and Erizas® (dexamethasone cipecilate). Hence, this review tries to understand why nasal powder formulations are still less common than liquid ones by analyzing whether this depends on the lack of (i) real evidence of superior therapeutic benefit of powders, (ii) therapeutic and/or commercial interest, (iii) efficient manufacturing methods or (iv) availability of suitable and affordable delivery devices. To this purpose, the reader's attention will be guided through nasal powder formulation strategies and manufacturing techniques, eventually giving up-to-date evidences of therapeutic efficacy in vivo. Advancements in the technology of insufflation devices will also be provided as nasal drug products are typical drug-device combinations.
Publisher: Elsevier BV
Date: 03-2010
DOI: 10.1016/J.JCONREL.2009.11.013
Abstract: In this study, clobetasol-17-propionate (CP) loaded lecithin/chitosan nanoparticles were studied with special attention to the transport of the active agent across the skin in vitro. Nanoparticles were characterized by measuring particle size, zeta potential, polydispersity index and encapsulation efficiency. The morphology of nanoparticles was evaluated by transmission electron microscopy. Encapsulation experiments with CP showed high encapsulation efficiency (92.2%). To assess the advantages of this carrier-based formulation in topical administration, the accumulation in and permeation across pig ear skin were compared with chitosan gel and commercially available cream of CP. The results obtained indicate that the incorporation of drug into nanoparticles induced an accumulation of CP especially in the epidermis without any significant permeation across the skin. Dilution of CP loaded nanoparticles with chitosan gel (1:9) produced the same amount of CP in the skin compared with commercial cream, although the former contained ten times less CP. This is a remarkable point for the reduction of the side effects of CP. These results demonstrated the suitability of lecithin/chitosan nanoparticles to induce epidermal targeting and to improve the risk-benefit ratio for topically applied CP.
Publisher: Wiley
Date: 28-03-2011
Publisher: Informa UK Limited
Date: 07-05-2017
DOI: 10.1080/03639045.2017.1321659
Abstract: The aim of this work was to develop an amorphous solid dispersions/solutions (ASD) of a poorly soluble drug, budesonide (BUD) with a novel polymer Soluplus The small volume of fluid present in the nasal cavity limits the absorption of a poorly soluble drug. Budesonide is a corticosteroid, practically insoluble and normally administered as a suspension-based nasal spray. The formulation was prepared through freeze-drying of polymer-drug solution. The formulation was assessed for its physicochemical (specific surface area, calorimetric analysis and X-ray powder diffraction), release properties and aerodynamic properties as well as transport in vitro using RPMI 2650 nasal cells, in order to elucidate the efficacy of the Soluplus-BUD formulation. The freeze-dried Soluplus-BUD formulation (LYO) showed a porous structure with a specific surface area of 1.4334 ± 0.0178 m Soluplus has been shown to be a promising polymer for the formulation of BUD amorphous solid suspension/solution. This opens up opportunities to develop new formulations of poorly soluble drug for nasal delivery.
Publisher: Springer Science and Business Media LLC
Date: 09-01-2009
DOI: 10.1007/S11095-008-9803-0
Abstract: The aim of this review is to provide the reader general and inspiring prospects on recent and promising fields of innovation in oral drug delivery. Nowadays, inventive drug delivery systems vary from geometrically modified and modular matrices, more close to "classic" pharmaceutical manufacturing processes, to futuristic bio micro-electro-mechanical systems (bioMEMS), based on manufacturing techniques borrowed from electronics and other fields. In these technologies new materials and creative solutions are essential designing intelligent drug delivery systems able to release the required drug at the proper body location with the correct release rate. In particular, oral drug delivery systems of the future are expected to have a significant impact on the treatment of diseases, such as AIDS, cancer, malaria, diabetes requiring complex and multi-drug therapies, as well as on the life of patients, whose age and/or health status make necessary a multiple pharmacological approach.
Publisher: Elsevier BV
Date: 12-2015
Publisher: Elsevier BV
Date: 11-2016
Publisher: MDPI AG
Date: 26-12-2016
DOI: 10.3390/IJMS18010032
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.IJPHARM.2018.06.006
Abstract: The purpose of this work was to study a new dry powder inhaler (DPI) of tobramycin capable to simplify the dose administration maneuvers to maximize the cystic fibrosis (CF) patient care in antibiotic inhalation therapy. For the purpose, tobramycin/sodium stearate powder (TobraPS) having a high drug content, was produced by spray drying, characterized and the aerodynamic behavior was investigated in vitro using different RS01 DPI inhalers. The aerosols produced with 28, 56 or 112 mg of tobramycin in TobraPS powder using capsules size #3, #2 or #0 showed that there was quasi linear relationship between the amount loaded in the device and the FPD. An in vivo study in healthy human volunteers showed that 3-6 inhalation acts were requested by the volunteers to inhale 120 mg of TobraPS powder loaded in a size #0 capsule aerosolized with a prototype RS01 device, according to their capability to inhale. The amount of powder emitted at 4 kPa pressure drop at constant air flow well correlated with the in vivo emission at dynamic flow, when the same volume of air passed through the device. The novel approach for the administration of 112 mg of tobramycin in one capsule could improve the convenience and adherence of the CF patient to the antibiotic therapy.
Publisher: Elsevier BV
Date: 05-2013
DOI: 10.1016/J.JCONREL.2013.02.009
Abstract: Tamoxifen citrate (TAM), an anticancer drug with hiphilic properties, was loaded in lecithin/chitosan nanoparticles (LCN) with a view to oral administration. The influence of tamoxifen loading on the physico-chemical properties of nanoparticles was studied. Size, surface charge and morphological properties of tamoxifen-loaded nanoparticles (LCN-TAM) were assessed. The increase in the tamoxifen amount in the LCN-TAM preparation up to 60 mg/100 ml maintained the positive zeta potential value of about +45 mV. A statistically significant decrease in particle size was observed for TAM amounts between 5 and 20mg. A strong influence of loaded tamoxifen on the structure of lecithin/chitosan nanoparticles was observed, supported by the quantification of free chitosan and morphological analysis. A loading of tamoxifen in nanoparticles of around 19% was obtained. The release of the drug from the LCN-TAM colloidal dispersion was measured, showing that tamoxifen citrate was released very slowly in simulated gastro-intestinal fluids without enzymes. When enzymes able to dismantle the nanoparticle structure were added to the dissolution medium, drug release was triggered and continued in a prolonged manner. Tamoxifen-loaded nanoparticles showed cytotoxicity towards MCF-7 cells comparable to that obtained with tamoxifen citrate solution, but the rate of this toxic effect was dependent on drug release. Caco-2 cells, used as a model of the intestinal epithelium, were shown to take up the TAM loaded nanoparticles extensively.
Publisher: Elsevier BV
Date: 2014
DOI: 10.1016/J.EJPS.2013.08.009
Abstract: The aim of the present research was to investigate the possibility to obtain by spray drying an insulin pulmonary powder respirable and stable at room temperature without the use of excipients. Several insulin spray-dried powders were prepared with or without the addition of excipients (mannitol, bovine serum albumin, aspartic acid) from water dispersions or from acidic aqueous solutions. Each formulation was characterized using laser diffraction, scanning electron microscopy and in vitro aerosol performance with a Turbospin DPI device. Stability was assessed by the quantification of impurities with a molecular mass greater than that of insulin (HMWP) and related proteins (A21+ORP). Insulin powders prepared without excipients from an acid solution showed a shrivelled, raisin-like shape of non-aggregated microparticles and a high respirability (FPF>65%). The optimal result with respect to respirability and stability was reached when the pH of the insulin acetic acid solution to spray dry was adjusted at pH 3.6 with ammonium hydroxide. The median volume diameter of the obtained powder was 4.04 μm, insulin content 95%, emitted dose of 89.5%, MMAD 1.79 μm and fine particle fraction of 83.6%. This powder was stable at room temperature over a period of eighteen months with respect to the content of A21+ORP. As far as the HMWP content was concerned, the powder complied with the specification limits for a period of five months. The insulin acetic powder opens up the possibility of a more effective pulmonary therapy less dependent on refrigerated storage.
Publisher: MDPI AG
Date: 13-10-2018
DOI: 10.3390/NANO8100825
Abstract: Lipid-based drugs are emerging as an interesting class of novel anticancer drugs with the potential to target specific cancer cell metabolic pathways linked to their proliferation and invasiveness. In particular, ω-3 polyunsaturated fatty acids (PUFA) derivatives such as epoxides and their bioisosteres have demonstrated the potential to suppress growth and promote apoptosis in triple-negative human breast cancer cells MDA-MB-231. In this study, 16-(4′-chloro-3′-trifluorophenyl)carbamoylamino]hexadecanoic acid (ClFPh-CHA), an anticancer lipid derived from ω-3,17,18-epoxyeicosanoic acid, was formulated as a stable nanoemulsion with size around 150 nm and narrow droplet size distribution (PDI 0.200) through phase-inversion emulsification process followed by high pressure homogenization in view of an oral administration. The ClFPh-CHA-loaded nanoemulsions were able to significantly decrease the relative tumor volume in mice bearing an intramammary tumor xenograft at all doses tested (2.5, 10 and 40 mg/kg) after 32 days of daily oral administration. Furthermore, absolute tumor weight was decreased to 50% of untreated control at 10 and 40 mg/kg, while intraperitoneal administration could achieve a significant reduction only at the highest dose of 40 mg/kg. Results suggest that oral administration of ClFPh-CHA formulated as a nanoemulsion has a sufficient bioavailability to provide an anticancer effect in mice and that the activity is at least equal if not superior to that obtained by a conventional parenteral administration of equivalent doses of the same drug.
Publisher: American Chemical Society (ACS)
Date: 24-09-2008
DOI: 10.1021/LA801992T
Abstract: The combined use of cryo-TEM, dynamic light scattering, and small-angle X-ray and neutron scattering techniques allows a detailed structural model of complex pharmaceutical preparations of soybean lecithin/chitosan nanoparticles used as drug vectors to be worked out. Charge-driven self-organization of the lipid(-) olysaccharide(+) vesicles occurs during rapid injection, under mechanical stirring, of an ethanol solution of soybean lecithin into a chitosan aqueous solution. We conclude that beyond the charge inversion region of the phase diagram, i.e., entering the redissolution region, the initial stages of particle formation are likely to be affected by a re-entrant condensation effect at the nanoscale. This behavior resembles that at the mesoscale which is well-known for polyion/ hiphile systems. Close to the boundary of the charge inversion region, nanoparticle formation occurs under a maximum condensation condition at the nanoscale and the complexation-aggregation process is driven toward a maximum multilamellarity. Interestingly, the formulation that maximizes vesicle multilamellarity corresponds to that displaying the highest drug loading efficiency.
Publisher: Oxford University Press (OUP)
Date: 03-2010
DOI: 10.1016/J.EJCTS.2009.08.012
Abstract: This study aims to investigate the effect of intrapleural polymeric films containing cisplatin on the local recurrence of malignant pleural mesothelioma in a rat tumour model. An orthotopic rat recurrence model of malignant pleural mesothelioma was used. Five animals per group were evaluated. Polymeric films (4.5 cm diameter) for the local delivery of anticancer drug were constructed: hyaluronate, chitosan and the combined dual-layer polymers were loaded with cisplatin at a concentration of 100 mgm(-2). Animals without any adjuvant therapy were used as control. Mesothelioma cells were injected subpleurally in the anaesthetised rats. Six days later, a pleural tumour of 5.5mm was resected and a left pneumonectomy and pleural abrasion were performed. Thereafter, the cisplatin-loaded and unloaded films or cisplatin solution were intrapleurally applied, according to randomisation. After 6 days, animals were euthanised and organs harvested for morphological and histological evaluations. The primary endpoint was the volume of tumour recurrence. The secondary endpoints were treatment-related toxicity cisplatin serum concentration evaluated at different time points and cisplatin concentration in the pleura measured at autopsy. Analysis of variance (ANOVA) was used for statistical analysis. Bonferroni correction was applied for comparison between all groups. Tumour volume was significantly reduced in the hyaluronate cisplatin and hyaluronate-chitosan cisplatin groups in comparison to control groups (p=0.001 and p<0.0001, respectively). Animals treated with hyaluronate-chitosan cisplatin had a tumour recurrence significantly lesser than animals treated with cisplatin solution (p=0.003) and hyaluronate cisplatin (p=0.032). No toxicity related to the different treatments was observed. On postoperative days 1 and 2, cisplatin was detected in the serum at a concentration six- and sevenfold significantly higher in the hyaluronate cisplatin and hyaluronate-chitosan cisplatin groups, in comparison to cisplatin solution, and was maintained over time. Cisplatin levels in the pleura were higher in the hyaluronate-chitosan cisplatin group than in all others. Hyaluronate-chitosan cisplatin was significantly effective in reducing tumour recurrence compared with cisplatin solution. Hyaluronate and hyaluronate-chitosan loaded with cisplatin assured significantly higher and more prolonged plasmatic drug concentrations than cisplatin solution without increasing toxicity.
Publisher: American Chemical Society (ACS)
Date: 09-2005
DOI: 10.1021/BC050050Z
Abstract: New folate-conjugated superparamagnetic maghemite nanoparticles have been synthesized for the intracellular hyperthermia treatment of solid tumors. These ultradispersed nanosystems have been characterized for their physicochemical properties and tumor cell targeting ability, facilitated by surface modification with folic acid. Preliminary experiments of nanoparticles heating under the influence of an alternating magnetic field at 108 kHz have been also performed. The nanoparticle size, surface charge, and colloidal stability have been assessed in various conditions of ionic strength and pH. The ability of these folate "decorated" maghemite nanoparticles to recognize the folate receptor has been investigated both by surface plasmon resonance and in folate receptor expressing cell lines, using radiolabeled folic acid in competitive binding experiments. The specificity of nanoparticle cellular uptake has been further investigated by transmission electron microscopy after incubation of these nanoparticles in the presence of three cell lines with differing folate receptor expression levels. Qualitative and quantitative determinations of both folate nanoparticles and nontargeted control nanoparticles demonstrated a specific cell internalization of the folate superparamagnetic nanoparticles.
Publisher: Elsevier BV
Date: 11-2006
Publisher: Bentham Science Publishers Ltd.
Date: 29-03-2014
DOI: 10.2174/1568026614666140329232252
Abstract: Statins are effective lipid lowering agents traditionally used for the primary and secondary prevention of cardiovascular disease. Statins also exert a range of pleiotropic effects that make them attractive candidates for use in a wide range of disorders, in particular inflammatory and immune mediated conditions. However, the exploitation of such pleiotropic effects has been greatly hindered by poor bioavailability and adverse effects on muscles and the liver at higher doses. Nanotechnology is often suggested as the solution to this problem, as it enables an increased bioavailability of statins. Moreover, colloidal carriers can offer targeted drug delivery approaches that enable localised biological effects of statins, further reducing their potential for unwanted toxicity and adverse effects. This article reviews the available evidences for the increased potential of statin therapy when administered in nano-formulations such as nanocrystals, nanoparticles, liposomes, micelles and various nano-enabled devices.
Publisher: IOP Publishing
Date: 19-02-2008
Publisher: MDPI AG
Date: 26-11-2019
DOI: 10.3390/MOLECULES24234312
Abstract: Glioblastoma (GBM) is the most lethal form of brain tumor, being characterized by the rapid growth and invasion of the surrounding tissue. The current standard treatment for glioblastoma is surgery, followed by radiotherapy and concurrent chemotherapy, typically with temozolomide. Although extensive research has been carried out over the past years to develop a more effective therapeutic strategy for the treatment of GBM, efforts have not provided major improvements in terms of the overall survival of patients. Consequently, new therapeutic approaches are urgently needed. Overcoming the blood–brain barrier (BBB) is a major challenge in the development of therapies for central nervous system (CNS) disorders. In this context, the intranasal route of drug administration has been proposed as a non-invasive alternative route for directly targeting the CNS. This route of drug administration bypasses the BBB and reduces the systemic side effects. Recently, several formulations have been developed for further enhancing nose-to-brain transport, mainly with the use of nano-sized and nanostructured drug delivery systems. The focus of this review is to provide an overview of the strategies that have been developed for delivering anticancer compounds for the treatment of GBM while using nasal administration. In particular, the specific properties of nanomedicines proposed for nose-to-brain delivery will be critically evaluated. The preclinical and clinical data considered supporting the idea that nasal delivery of anticancer drugs may represent a breakthrough advancement in the fight against GBM.
Publisher: MDPI AG
Date: 19-06-2020
DOI: 10.3390/PHARMACEUTICS12060568
Abstract: Drug administration to the vaginal site has gained increasing attention in past decades, highlighting the need for reliable in vitro methods to assess the performance of novel formulations. To optimize formulations destined for the vaginal site, it is important to evaluate the drug retention within the vagina as well as its permeation across the mucosa, particularly in the presence of vaginal fluids. Herewith, the vaginal-PVPA (Phospholipid Vesicle-based Permeation Assay) in vitro permeability model was validated as a tool to evaluate the permeation of the anti-inflammatory drug ibuprofen from liposomal formulations (i.e., plain and chitosan-coated liposomes). Drug permeation was assessed in the presence and absence of mucus and simulated vaginal fluid (SVF) at pH conditions mimicking both the healthy vaginal premenopausal conditions and vaginal infection re-puberty ost-menopause state. The permeation of ibuprofen proved to depend on the type of formulation (i.e., chitosan-coated liposomes exhibited lower drug permeation), the mucoadhesive formulation properties and pH condition. This study highlights both the importance of mucus and SVF in the vaginal model to better understand and predict the in vivo performance of formulations destined for vaginal administration, and the suitability of the vaginal-PVPA model for such investigations.
Publisher: MDPI AG
Date: 22-08-2020
DOI: 10.3390/NANO10091650
Abstract: Biphasic oil/water nanoemulsions have been proposed as delivery systems for the intranasal administration of curcumin (CUR) and quercetin (QU), due to their high drug entrapment efficiency, the possibility of simultaneous drug administration and protection of the encapsulated compounds from degradation. To better understand the physicochemical and biological performance of the selected formulation simultaneously co-encapsulating CUR and QU, a stability test of the compound mixture was firstly carried out using X-ray powder diffraction and thermal analyses, such as differential scanning calorimetry (DSC) and thermogravimetric analyses (TGA). The determination and quantification of the encapsulated active compounds were then carried out being an essential parameter for the development of innovative nanomedicines. Thus, a new HPLC–UV/Vis method for the simultaneous determination of CUR and QU in the nanoemulsions was developed and validated. The X-ray diffraction analyses demonstrated that no interaction between the mixture of active ingredients, if any, is strong enough to take place in the solid state. Moreover, the thermal analysis demonstrated that the CUR and QU are stable in the nanoemulsion production temperature range. The proposed analytical method for the simultaneous quantification of the two actives was selective and linear for both compounds in the range of 0.5–12.5 µg/mL (R2 0.9997), precise (RSD below 3%), robust and accurate (recovery 100 ± 5 %). The method was validated in accordance with ICH Q2 R1 “Validation of Analytical Procedures” and CDER-FDA “Validation of chromatographic methods” guideline. Furthermore, the low limit of detection (LOD 0.005 µg/mL for CUR and 0.14 µg/mL for QU) and the low limit of quantification (LOQ 0.017 µg/mL for CUR and 0.48 µg/mL for QU) of the method were suitable for the application to drug release and permeation studies planned for the development of the nanoemulsions. The method was then applied for the determination of nanoemulsions CUR and QU encapsulation efficiencies ( 99%), as well as for the stability studies of the two compounds in simulated biological fluids over time. The proposed method represents, to our knowledge, the only method for the simultaneous quantification of CUR and QU in nanoemulsions.
Publisher: MDPI AG
Date: 28-10-2021
DOI: 10.3390/MOLECULES26216507
Abstract: Tamoxifen citrate (TMC), a non-steroidal antiestrogen drug used for the treatment of breast cancer, was loaded in a block copolymer of maltoheptaose-b-polystyrene (MH-b-PS) nanoparticles, a potential drug delivery system to optimize oral chemotherapy. The nanoparticles were obtained from self-assembly of MH-b-PS using the standard and reverse nanoprecipitation methods. The MH-b-PS@TMC nanoparticles were characterized by their physicochemical properties, morphology, drug loading and encapsulation efficiency, and release kinetic profile in simulated intestinal fluid (pH 7.4). Finally, their cytotoxicity towards the human breast carcinoma MCF-7 cell line was assessed. The standard nanoprecipitation method proved to be more efficient than reverse nanoprecipitation to produce nanoparticles with small size and narrow particle size distribution. Moreover, tamoxifen-loaded nanoparticles displayed spherical morphology, a positive zeta potential and high drug content (238.6 ± 6.8 µg mL−1) and encapsulation efficiency (80.9 ± 0.4 %). In vitro drug release kinetics showed a burst release at early time points, followed by a sustained release profile controlled by diffusion. MH-b-PS@TMC nanoparticles showed higher cytotoxicity towards MCF-7 cells than free tamoxifen citrate, confirming their effectiveness as a delivery system for administration of lipophilic anticancer drugs.
Publisher: Informa UK Limited
Date: 30-08-2019
DOI: 10.1080/03639045.2019.1652636
Abstract: Colistimethate sodium (CMS) for treatment of lung infections in cystic fibrosis patient was transformed into a dry powder for inhalation by spray drying. Design of Experiment was applied for understanding the role of the spray-drying process parameters on the critical quality attributes of the CMS spray-dried (SD) powders and agglomerates thereof. Eleven experimental SD microparticle powders were constructed under different process conditions according to a central composite design. The SD microparticles were then agglomerated in soft pellets. Eleven physico-chemical characteristics of SD CMS microparticle powders or agglomerates thereof were selected as critical quality attributes. The yield of SD process was higher than 75%. The emitted fraction of agglomerates from RS01 inhaler was 75-84%, and the fine particle fraction (particles <5 µm) was between 58% and 62%. The quality attributes of CMS SD powders and respective agglomerates that were significantly influenced by spray-drying process parameters were residual solvent and drug content of the SD microparticles as well as bulk density and respirable dose of the agglomerates. These attributes were also affected by the combination of the process variables. The air aspiration rate was found as the most positively influential on drug and solvent content and respirable dose. The residual solvent content significantly influenced the powder bulk properties and aerodynamic behavior of the agglomerates, i.e. quality attributes that govern drug metering in the device and the particles lungs deposition. Agglomerates of CMS SD microparticles, in combination with RS01 DPI, showed satisfactory results in terms of dose emitted and fine particle fraction.
Publisher: Elsevier BV
Date: 2013
DOI: 10.1016/J.IJPHARM.2012.09.049
Abstract: In the present study, a nasal powder of the antidiuretic peptide desmopressin (DDAVP) formulated as chimera agglomerates was studied to improve drug bioavailability and provide a flexible drug product. Firstly, DDAVP was spray-dried along with mannitol and lecithin to produce primary microparticles capable of instantaneous dissolution in water. The chimera agglomerates were spontaneously formed by mechanically vibrating the microparticles on two stacked sieves. Agglomerate formation and strength were favored by the presence of lecithin. Drug content and dissolution rate remained unmodified after agglomeration. However, owing to the agglomerate larger size, powder flowability was greatly improved in comparison with the original microparticles, allowing accurate powder dosing into the nasal delivery device. DDAVP in vitro permeation across excised rabbit nasal mucosa from the agglomerates was significantly higher than that obtained from a commercial liquid nasal spray. In rats, intranasal DDAVP agglomerates allowed for efficient administration with almost 80% of the loaded powder emitted from the device into the animal nose. The administration of DDAVP agglomerates induced a significant reduction in urine production. Moreover, the antidiuretic effect of agglomerates did not significantly differ from the one induced by an intravenous injection of DDAVP at a ten-fold lower dose.
Publisher: Informa UK Limited
Date: 03-08-2023
Publisher: American Chemical Society (ACS)
Date: 25-08-2004
DOI: 10.1021/BC034186D
Abstract: The tumor targeting properties of a new drug carrier synthesized by bioconjugation of folic acid (FA) to beta-cyclodextrins through a poly(ethylene glycol) (PEG) spacer (CD-PEG-FA) were investigated. Surface plasmon resonance demonstrated that CD-PEG-FA specifically interacts with immobilized folate binding protein (FBP) while the naked beta-cyclodextrins do not display any specific interaction. In vitro studies demonstrated that CD-PEG-FA was devoid of cell toxicity. [(3)H]-folic acid/CD-PEG-FA competition binding investigations performed with folate receptor overexpressing human epidermal carcinoma KB cells showed that CD-PEG-FA had about 14 times lower tumor cell binding capacity than free folic acid. The carrier cell trafficking properties were investigated using rhodamine-B as fluorescent probe, which possesses 3000 and 4580 M(-)(1) inclusion constants for CD-PEG-FA and beta-cyclodextrins, respectively. Cell-associated fluorescence measurements showed that CD-PEG-FA does not promote the rhodamine-B uptake into non-folate receptor expressing human lung carcinoma MCF7 cells while 19% higher accumulation in KB cells was found with respect to rhodamine-B loaded beta-cyclodextrins. Confocal laser scanning microscopy indicated the presence of cytosolic red fluorescent spots after 2 h of incubation of KB cells with rhodamine-B included CD-PEG-FA. The fluorescent dye resided primarily in small spots, namely, endosomes and multivesicular bodies. At 1 h after pulsed incubation, wider red fluorescent cellular structures appeared as a fusion of previous structures.
Publisher: MDPI AG
Date: 30-09-2020
DOI: 10.20944/PREPRINTS202009.0745.V1
Abstract: Polyhydroxyalkanoate (PHA) co-polymers show relatively higher in vivo degradation rate compared to other PHAs thus they received a great deal of attention for a wide range of medical applications. Nanoparticles (NPs) loaded with poorly water soluble anticancer drug docetaxel (DCX) were produced using poly 3-hydroxybutyrate-co-4-hydroxybutyrate, P(3HB-co-4HB), co-polymers biosynthesised from Cupriavidus sp. USMAA1020 isolated from Malaysian environment. Three co-polymers with different molar proportions of 4-hydroxybutirate (4HB) were used: 16% (PHB16), 30% (PHB30) and 70% (PHB70) 4HB-containing P(3HB-co-4HB). Blank and DCX loaded nanoparticles were then characterized for their size and size distribution, surface charge, encapsulation efficiency and drug release. Pre-formulation studies showed that an optimised formulation could be achieved through the emulsification/solvent evaporation method using PHB70 with the addition of 1.0% PVA, as stabilizer and 0.03% VitE-TPGS, as surfactant. DCX-loaded PHB70 nanoparticles (DCX-PHB70) gave the desired particle size distribution in term of average particles sizes around 150 nm and narrow particle size distribution (PDI below 0.100). The encapsulation efficiencies result showed that at 30% w/w drug-to-polymer ratio: DCX- PHB16 NPs were able to encapsulate up to 42% of DCX DCX-PHB30 NPs encapsulated up to 46% of DCX and DCX-PHB70 NPs encapsulated up to 50% of DCX within the nanoparticles system. Approximately 60% of DCX was released from the DCX-PHB70 NPs within 7 days for 5%, 10% and 20% of drug to polymer ratio while for the 30% and 40% drug to polymer ratios, an almost complete drug release (98%) after 7 days of incubation was observed.
Publisher: Informa UK Limited
Date: 29-05-2014
DOI: 10.3109/17435390.2014.918203
Abstract: Aggregates of multiwalled carbon nanotubes (MWCNT) impair the barrier properties of human airway cell monolayers. To resolve the mechanism of the barrier alteration, monolayers of Calu-3 human airway epithelial cells were exposed to aggregated MWCNT. At the cell-population level, trans-epithelial electrical resistance (TEER) was used as an indicator of barrier competence, caspase activity was assessed with standard biochemical assays, and cell viability was investigated by biochemical techniques and high-throughput screening (HTS) technique based on automated epifluorescence microscopy. At cell level, the response to MWCNT was investigated with confocal microscopy, by evaluating cell death (calcein ropidium iodide (PI)), proliferation (Ki-67), and apoptosis (caspase activity). At the cell-population level, exposure to aggregated MWCNT caused a decrease in TEER, which was not associated with a decrease in cell viability or onset of apoptosis even after an 8-d exposure. In contrast, confocal imaging demonstrated contact with MWCNT aggregates triggered cell death after 24 h of exposure. In the presence of a natural surfactant, both TEER decrease and contact-mediated toxicity were mitigated. With confocal imaging, increased proliferation and apoptosis were detected in Calu-3 cells next to the aggregates. Contact-mediated cytotoxicity was recorded in two additional cell lines (BEAS-2B and A549) derived from human airways. Similar results were confirmed by adopting two additional MWCNT preparations with different physico-chemical features. This indicates MWCNT caused localized damage to airway epithelial monolayers in vitro and altered the apoptotic and proliferative rate of epithelial cells in close proximity to the aggregates. These findings provide evidence on the pathway by which MWCNT aggregates impair airway barrier function, and support the use of imaging techniques as a possible regulatory-decision supporting tool to identify effects of aggregated nanomaterials not readily detected at cell population level.
Publisher: MDPI AG
Date: 02-08-2020
DOI: 10.20944/PREPRINTS202008.0025.V1
Abstract: Biphasic oily/water nanoemulsions have been proposed as delivery systems for the intranasal administration of curcumin (CUR) and quercetin (QU), due to their high drug entrapment efficiency, the possibility of simultaneous drug administration and protection of the encapsulated compounds from the degradation. To better understand the physicochemical and biological performance of the selected formulation simultaneously co-encapsulating CUR and QU, a stability test of the compounds mixture was firstly carried out using X-ray powder diffraction and thermal analyses, such as differential scanning calorimetry (DSC) and thermogravimetric analyses (TGA). The determination and quantification of the encapsulated active compounds was then required being an essential tool for the development of innovative nanomedicines. Thus, a new HPLC& ndash UV/Vis method for the simultaneous determination of CUR and QU in the nanoemulsions and their evaluation in stability studies in simulated biological fluids was developed and validated. The X-ray diffraction analyses demonstrated that no interaction between the mixture of active ingredients, if any, is strong enough to take place in the solid state. Moreover, the thermal analysis demonstrated that the CUR and QU are stable in the nanoemulsion production temperature range. The proposed analytical method for the simultaneous quantification of the two actives was selective and linear for both compounds in the range of 0.5 & ndash 12.5 & micro g/mL (R2 & 0.9997), precise (RSD below 3%), robust and accurate (recovery 100 & lusmn 5 %). The method was validated in accordance with ICH Q2 R1 & Validation of Analytical Procedures& and CDER-FDA 2validation of chromatographic methods& guideline. Furthermore, the low detection (LOD & 0.005 & micro g/mL for CUR and & .14 & micro g/mL for QU) and quantification limits (LOQ & 0.017 & micro g/mL for CUR and & 0.48 & micro g/mL for QU) of the method were suitable for the application to drug release and permeation studies planned for the development of the nanoemulsions. The method was then applied for the determination of nanoemulsions CUR and QU encapsulation efficiencies (& 99%), as well as for the stability studies of the two compounds in simulated biological fluids over time. The proposed method represents, to our knowledge, the only method for the simultaneous quantification of CUR, and QU in nanoemulsions.
Publisher: Elsevier BV
Date: 2013
Publisher: MDPI AG
Date: 11-2021
DOI: 10.3390/PHARMACEUTICS13111825
Abstract: Inhalation of Calcium Phosphate nanoparticles (CaPs) has recently unmasked the potential of this nanomedicine for a respiratory lung-to-heart drug delivery targeting the myocardial cells. In this work, we investigated the development of a novel highly respirable dry powder embedding crystalline CaPs. Mannitol was selected as water soluble matrix excipient for constructing respirable dry microparticles by spray drying technique. A Quality by Design approach was applied for understanding the effect of the feed composition and spraying feed rate on typical quality attributes of inhalation powders. The in vitro aerodynamic behaviour of powders was evaluated using a medium resistance device. The inner structure and morphology of generated microparticles were also studied. The 1:4 ratio of CaPs/mannitol led to the generation of hollow microparticles, with the best aerodynamic performance. After microparticle dissolution, the released nanoparticles kept their original size.
Publisher: Elsevier BV
Date: 06-2020
Publisher: Hindawi Limited
Date: 2014
DOI: 10.1155/2014/641590
Abstract: Burns are serious traumas related to skin damage, causing extreme pain and possibly death. Natural drugs such as Aloe vera and vitamin E have been demonstrated to be beneficial in formulations for wound healing. The aim of this work is to develop and evaluate polymeric films containing Aloe vera and vitamin E to treat wounds caused by burns. Polymeric films containing different quantities of sodium alginate and polyvinyl alcohol (PVA) were characterized for their mechanical properties and drug release. The polymeric films, which were produced, were thin, flexible, resistant, and suitable for application on damaged skin, such as in burn wounds. Around 30% of vitamin E acetate was released from the polymeric films within 12 hours. The in vivo experiments with tape stripping indicated an effective accumulation in the stratum corneum when compared to a commercial cream containing the same quantity of vitamin E acetate. Vitamin E acetate was found in higher quantities in the deep layers of the stratum corneum when the film formulation was applied. The results obtained show that the bioadhesive films containing vitamin E acetate and Aloe vera could be an innovative therapeutic system for the treatment of burns.
Publisher: MDPI AG
Date: 05-2019
DOI: 10.3390/PHARMACEUTICS11050203
Abstract: Tuberculosis resistant cases have been estimated to grow every year. Besides Mycobacterium tuberculosis, other mycobacterial species are responsible for an increasing number of difficult-to-treat infections. To increase efficacy of pulmonary treatment of mycobacterial infections an inhalable antibiotic powder targeting infected alveolar macrophages (AMs) and including an efflux pump inhibitor was developed. Low molecular weight sodium hyaluronate sub-micron particles were efficiently loaded with rif icin, isoniazid and verapamil, and transformed in highly respirable microparticles (mean volume diameter: 1 μm) by spray drying. These particles were able to regenerate their original size upon contact with aqueous environment with mechanical stirring or sonication. The in vitro drugs release profile from the powder was characterized by a slow release rate, favorable to maintain a high drug level inside AMs. In vitro antimicrobial activity and ex vivo macrophage infection assays employing susceptible and drug resistant strains were carried out. No significant differences were observed when the powder, which did not compromise the AMs viability after a five-day exposure, was compared to the same formulation without verapamil. However, both preparations achieved more than 80% reduction in bacterial viability irrespective of the drug resistance profile. This approach can be considered appropriate to treat mycobacterial respiratory infections, regardless the level of drug resistance.
Publisher: Elsevier BV
Date: 07-2020
Publisher: Informa UK Limited
Date: 03-08-2023
Publisher: Springer Science and Business Media LLC
Date: 24-05-2013
Publisher: Informa UK Limited
Date: 20-11-2015
DOI: 10.3109/10717544.2015.1114047
Abstract: Lung cancer poses one of the most significant challenges to modern medicine, killing thousands every year. Current therapy involves surgical resection supplemented with chemotherapy and radiotherapy due to high rates of relapse. Shortcomings of currently available chemotherapy protocols include unacceptably high levels of systemic toxicity and low accumulation of drug at the tumor site. Loco-regional delivery of nanocarriers loaded with anticancer agents has the potential to significantly increase efficacy, while minimizing systemic toxicity to anticancer agents. Local drug administration at the tumor site using nanoparticulate drug delivery systems can reduce systemic toxicities observed with intravenously administered anticancer drugs. In addition, this approach presents an opportunity for sustained delivery of anticancer drug over an extended period of time. Herein, the progress in the development of locally administered nanomedicines for the treatment of lung cancer is reviewed. Administration by inhalation, intratumoral injection and means of direct in situ application are discussed, the benefits and drawbacks of each modality are explored.
Publisher: MDPI AG
Date: 15-03-2018
Publisher: AME Publishing Company
Date: 2018
Publisher: Elsevier BV
Date: 2005
Publisher: Informa UK Limited
Date: 2005
DOI: 10.1080/03639040500216337
Abstract: The purpose of this study was to investigate the physico-chemical characteristics of sucralfate humid gel dried by microwaves, in relation to the residual water content. Differential scanning calorimetry (DSC) allowed for the determination of the water state in sucralfate s les. Fourier-transform infrared (FT-IR) spectroscopy was used to monitor the changes in sucralfate gel structure induced by the microwave drying. A boundary value of total water content for sucralfate gel s les was found at 42% (w/w). Below this value only bound water was present, whereas above this value, the increase in total water was due to free water. In the physical form of gel, the strength of the coordination between sulfate anions and the positively charged aluminum hydroxide was dependent on the residual water content. The study of the sedimentation behavior of water suspensions prepared with dried sucralfate allowed for the evaluation of the retention of gel properties. We found that the microwave drying process affected the sedimentation of sucralfate dried gel suspensions independent of the residual water content: when suspensions were prepared from sucralfate dried gel powders containing more than 42% (w/w) of residual water, the sedimentation ratio was higher than 0.9. The non-gel powder suspension showed a sedimentation ratio of 0.68 +/- 0.02, whereas the sucralfate humid gel suspension did not sediment.
Publisher: Elsevier BV
Date: 2004
Publisher: MDPI AG
Date: 17-11-2022
DOI: 10.3390/PHARMACEUTICS14112498
Abstract: Fluorescent organic nanoparticles (FONs) are a large family of nanostructures constituted by organic components that emit light in different spectral regions upon excitation, due to the presence of organic fluorophores. FONs are of great interest for numerous biological and medical applications, due to their high tunability in terms of composition, morphology, surface functionalization, and optical properties. Multifunctional FONs combine several functionalities in a single nanostructure (emission of light, carriers for drug-delivery, functionalization with targeting ligands, etc.), opening the possibility of using the same nanoparticle for diagnosis and therapy. The preparation, characterization, and application of these multifunctional FONs require a multidisciplinary approach. In this review, we present FONs following a tutorial approach, with the aim of providing a general overview of the different aspects of the design, preparation, and characterization of FONs. The review encompasses the most common FONs developed to date, the description of the most important features of fluorophores that determine the optical properties of FONs, an overview of the preparation methods and of the optical characterization techniques, and the description of the theoretical approaches that are currently adopted for modeling FONs. The last part of the review is devoted to a non-exhaustive selection of some recent biomedical applications of FONs.
Publisher: Elsevier BV
Date: 06-2015
DOI: 10.1016/J.IJPHARM.2015.04.003
Abstract: In this work three capsule-based dry powder inhalers, available for generics product development, were compared. Two technologically different dry powder formulations were used in order to relate the capsule piercing position and motion in the device to their aerodynamic performance. A "pierce and inhale" design, in which the capsules pierced with RS01, HandiHaler or Turbospin devices were aerosolized in the same device or transferred and aerosolized with another device, was constructed and carried out. The results obtained showed that two dry powder formulations, i.e., a drug/lactose blend or a carrier-free powder, aerosolized using capsule based inhalers, performed differently. The aerosolization of drug carrier mixture in terms of drug dispersion and emitted dose, was more sensible to the piercing and device combination than the carrier free powder. The motion of the capsule during the aerosolization boosted the powder emission, whereas the powder disaggregation was more influenced by the airflow pattern around the capsule and inside the inhaler turbulence chamber.
Publisher: Future Science Ltd
Date: 07-2017
Abstract: Statins are used for the primary and secondary prevention of cardiovascular disease by inhibiting cholesterol synthesis in the liver. Statins have also noncholesterol-related effects, called pleiotropic effects, which arise from statins’ anti-inflammatory, immunomodulatory and antioxidant properties. These effects are especially attractive for the treatment of various brain diseases ranging from stroke to neurodegenerative diseases. Still, low brain concentrations after oral drug administration hinder the clinical application of statins in these pathologies. Pharmaceutical nanotechnologies may offer a solution to this problem, as local or targeted delivery of nanoencapsulated statins may increase brain availability. This special report rapidly summarizes the potential of statins in the treatment of brain diseases and the pharmaceutical nanotechnologies that could provide a viable approach to enable these indications.
Publisher: Springer Science and Business Media LLC
Date: 31-12-2011
Publisher: Bentham Science Publishers Ltd.
Date: 10-02-2015
DOI: 10.2174/1568026615666150108150217
Abstract: Blindness and visual impairment affect millions of people worldwide and have a very important impact on patients quality of life. Proteins and peptides represent nowadays an important therapeutic tool for the treatment of ocular diseases but, despite their potential, have significant limitations, as the administration of protein-based pharmaceuticals represents a real challenge. Moreover, administration of ocular medications is difficult due to the peculiar structure of this organ and the presence of numerous barriers protecting the eye inner structure. Nanoencapsulation of peptides and proteins presents a number of advantages for their ocular delivery since it can protect the drug from metabolic activity, control and sustain the release and increase drug bioavailability after topical or intravitreal administration. In fact, nanoparticulate formulations are contributing to overcome ocular barriers, such as the corneal or the blood-retinal barrier, improve the residence time in the eye, increase local drug level, reduce the drug dosage and showing improved performance when compared to conventional formulations. Besides, proteins have also been proposed for the preparation of nanocarriers intended for ophthalmic administration, since they are highly biocompatible, biodegradable and easily modified to link surface ligands. The present review focuses the attention on the use of proteins in ocular drug delivery nanotechnology: their dual role as both therapeutics and carriers has been critically evaluated and discussed.
Publisher: The Royal Society of Chemistry
Date: 30-07-2012
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.JCONREL.2017.07.042
Abstract: In this work, a fixed-dose combination of gabapentin and flurbiprofen formulated as multilayer tablets has been designed, developed and studied in vitro and in vivo. The aim was to construct a single dosage form of the two drugs, able to perform a therapeutic program involving three release kinetics and two delivery sites, i.e., immediate release of gabapentin, intra-gastric prolonged release of gabapentin and intestinal (delayed) release of flurbiprofen. An oblong three-layer tablet was manufactured having as top layer a floating hydrophilic polymeric matrix for gastric release of gabapentin, as middle layer a disintegrating formulation for immediate release of a gabapentin loading dose and as bottom layer, an uncoated hydrophilic polymeric matrix, swellable but insoluble in gastric fluids, for delayed and prolonged release of flurbiprofen in intestinal environment. The formulations were studied in vitro and in vivo in healthy volunteers. The in vitro release rate assessment confirmed the programmed delivery design. A significant higher bioavailability of gabapentin administered 30min after meal, compared to fasting conditions or to dose administration 10min before meal, argued in favor of the gastro-retention of gabapentin prolonged release layer. The two drugs were delivered at different anatomical sites, since the food presence prolonged the gastric absorption of gabapentin from the floating layer and delayed the flurbiprofen absorption. The attainment of a successful delayed release of flurbiprofen was realized by a matrix based on a polymers' combination. The combined use of three hydrophilic polymers with different pH sensitivity provided the dosage form layer containing flurbiprofen with gastro-resistant characteristics without the use of film coating.
Publisher: Elsevier BV
Date: 04-2016
Publisher: Elsevier
Date: 2013
Publisher: MDPI AG
Date: 22-03-2023
DOI: 10.3390/PHARMACEUTICS15031023
Abstract: This work illustrates the development of a dry inhalation powder of cyclosporine-A for the prevention of rejection after lung transplantation and for the treatment of COVID-19. The influence of excipients on the spray-dried powder’s critical quality attributes was explored. The best-performing powder in terms of dissolution time and respirability was obtained starting from a concentration of ethanol of 45% (v/v) in the feedstock solution and 20% (w/w) of mannitol. This powder showed a faster dissolution profile (Weibull dissolution time of 59.5 min) than the poorly soluble raw material (169.0 min). The powder exhibited a fine particle fraction of 66.5% and an MMAD of 2.97 µm. The inhalable powder, when tested on A549 and THP-1, did not show cytotoxic effects up to a concentration of 10 µg/mL. Furthermore, the CsA inhalation powder showed efficiency in reducing IL-6 when tested on A549/THP-1 co-culture. A reduction in the replication of SARS-CoV-2 on Vero E6 cells was observed when the CsA powder was tested adopting the post-infection or simultaneous treatment. This formulation could represent a therapeutic strategy for the prevention of lung rejection, but is also a viable approach for the inhibition of SARS-CoV-2 replication and the COVID-19 pulmonary inflammatory process.
Publisher: Elsevier BV
Date: 03-2006
DOI: 10.1016/J.JCONREL.2005.12.006
Abstract: The aim of this paper was to study the applicability of the release module assemblage technology for an adaptable control of drug delivery rate and site. The elementary release module was a swellable matrix having one base convex and the other concave, named Dome Matrix. The swelling and release behavior of the release module was studied. The presence of the convex and concave bases in the swellable matrix slightly changed the overall drug delivery kinetics exhibited by a flat base cylindrical matrix having the same weight and composition. The swelling and drug release of the in idual bases of the matrix was also studied to investigate the effect of the surface shape. The concave, convex and flat bases exhibited different swelling and release kinetics. The convex base released drug at faster rate than the concave base, whereas the flat base was intermediate. The release mechanisms of convex and concave bases were significantly different. The Dome Matrix module was selected for assembling several modules in a delivery system obtained by a guided insertion of the convex base into the concave base or by concave/concave base sticking. The module assemblage shows different drug release behavior depending on the geometry of assembled systems.
Publisher: MDPI AG
Date: 18-02-2019
DOI: 10.3390/PHARMACEUTICS11020086
Abstract: Drug delivery to the brain represents a challenge, especially in the therapy of central nervous system malignancies. Simvastatin (SVT), as with other statins, has shown potential anticancer properties that are difficult to exploit in the central nervous system (CNS). In the present work the physico–chemical, mucoadhesive, and permeability-enhancing properties of simvastatin-loaded poly-ε-caprolactone nanocapsules coated with chitosan for nose-to-brain administration were investigated. Lipid-core nanocapsules coated with chitosan (LNCchit) of different molecular weight (MW) were prepared by a novel one-pot technique, and characterized for particle size, surface charge, particle number density, morphology, drug encapsulation efficiency, interaction between surface nanocapsules with mucin, drug release, and permeability across two nasal mucosa models. Results show that all formulations presented adequate particle sizes (below 220 nm), positive surface charge, narrow droplet size distribution (PDI 0.2), and high encapsulation efficiency. Nanocapsules presented controlled drug release and mucoadhesive properties that are dependent on the MW of the coating chitosan. The results of permeation across the RPMI 2650 human nasal cell line evidenced that LNCchit increased the permeation of SVT. In particular, the amount of SVT that permeated after 4 hr for nanocapsules coated with low-MW chitosan, high-MW chitosan, and control SVT was 13.9 ± 0.8 μg, 9.2 ± 1.2 µg, and 1.4 ± 0.2 µg, respectively. These results were confirmed by SVT ex vivo permeation across rabbit nasal mucosa. This study highlighted the suitability of LNCchit as a promising strategy for the administration of simvastatin for a nose-to-brain approach for the therapy of brain tumors.
Publisher: Informa UK Limited
Date: 30-01-2020
DOI: 10.1080/17425247.2020.1714589
Abstract: Nasal drug delivery has specific challenges which are distinct from oral inhalation, alongside which it is often considered. The next generation of nasal products will be required to deliver new classes of molecule, e.g. vaccines, biologics and drugs with action in the brain or sinuses, to local and systemic therapeutic targets. Innovations and new tools/knowledge are required to design products to deliver these therapeutic agents to the right target at the right time in the right patients. We report the outcomes of an expert meeting convened to consider gaps in knowledge and unmet research needs in terms of (i) formulation and devices, (ii) meaningful product characterization and modeling, (iii) opportunities to modify absorption and clearance. Important research questions were identified in the areas of device and formulation innovation, critical quality attributes for different nasal products, development of nasal casts for drug deposition studies, improved experimental models, the use of simulations and nasal delivery in special populations. We offer these questions as a stimulus to research and suggest that they might be addressed most effectively by collaborative research endeavors.
Publisher: Elsevier BV
Date: 04-2009
DOI: 10.1016/J.EJPS.2008.12.015
Abstract: Nasal spray products containing desmopressin acetate (DDAVP) were tested in vitro to evaluate the effect of the contained preservatives on drug permeation across rabbit nasal mucosa. Experiments were performed using Franz-type diffusion cells with rabbit nasal mucosa as model barrier. Transport profiles obtained in comparison with a preservative-free solution evidenced that in the presence of preservatives DDAVP permeation in vitro always increased (p<0.05), although at different extents (chlorobutanol<benzalkonium<sorbate). While for benzalkonium structural damage of the mucosa could occur decreasing its barrier properties, the effect of sorbate on drug transport was further investigated, being less studied. After having found that sorbate permeated together with DDAVP, the hypothesis that the two compounds formed an ion pair in solution with improved permeability was made. Additional experiments with aqueous test solutions reconstructed ad hoc containing desmopressin and varying sorbate concentrations confirmed the enhancing effect of sorbate, which however resulted to be independent of sorbate concentration. In conclusion, preservatives significantly enhanced desmopressin permeation in vitro across rabbit nasal mucosa with different mechanisms. If a correlation existed between these data and in vivo DDAVP bioavailability after nasal administration, this could strengthen the safety concerns related to the use of this medication in adults and children.
Publisher: MDPI AG
Date: 14-01-2022
DOI: 10.3390/PHARMACEUTICS14010194
Abstract: The nose-to-brain delivery of neuroprotective natural compounds is an appealing approach for the treatment of neurodegenerative diseases. Nanoemulsions containing curcumin (CUR) and quercetin (QU) were prepared by high-pressure homogenization and characterized physicochemically and structurally. A negative (CQ_NE−), a positive (CQ_NE+), and a gel (CQ_NEgel) formulation were developed. The mean particle size of the CQ_NE− and CQ_NE+ was below 120 nm, while this increased to 240 nm for the CQ_NEgel. The formulations showed high encapsulation efficiency and protected the CUR/QU from biological/chemical degradation. Electron paramagnetic resonance spectroscopy showed that the CUR/QU were located at the interface of the oil phase in the proximity of the surfactant layer. The cytotoxicity studies showed that the formulations containing CUR/QU protected human nasal cells from the toxicity evidenced for blank NEs. No permeation across an in vitro model nasal epithelium was evidenced for CUR/QU, probably due to their poor water-solubility and instability in physiological buffers. However, the nasal cells’ drug uptake showed that the total amount of CUR/QU in the cells was related to the NE characteristics (CQ_NE− CQ_NE+ CQ_NEgel). The method used allowed the obtainment of nanocarriers of an appropriate size for nasal administration. The treatment of the cells showed the protection of cellular viability, holding promise as an anti-inflammatory treatment able to prevent neurodegenerative diseases.
Publisher: Elsevier BV
Date: 02-2010
DOI: 10.1016/J.EJPB.2009.11.002
Abstract: Conventional formulations of chlorhexidine usually provide short-term efficiency, requiring repeated applications to maintain antibacterial activity. Therefore, appropriate release system of chlorhexidine controlling local drug delivery would reduce the number of applications and enhance patient compliance. The aim of this study was to develop a controlled release system based on medical polyurethane for the local delivery of chlorhexidine diacetate (CDA). CDA-loaded polyurethane films (CDA-Films) and CDA-loaded polyurethane sandwiches (CDA-Sandwiches) were obtained by casting and solvent evaporation. The physico-chemical aspects of CDA-loaded polyurethane systems were investigated, and the crystalline state of CDA in the polymeric system was highlighted. CDA-Films exhibited appropriate mechanical properties for further applications. Drug release was measured in two different media: (i) distilled water and (ii) physiological saline solution to mimic in vivo conditions. Drug release studies were performed up to 11days on CDA-Films and 29days for CDA-Sandwiches. Release of CDA depended on drug loading and the structure of the system. In particular, release of CDA from the sandwich system followed zero-order kinetic. The release rate was significantly lower in physiological solution. Antibacterial studies were carried out on CDA-Films against Staphylococcus aureus and Staphylococcus epidermidis showing 35days persisting antibacterial activity. In conclusion, the polyurethane-based system developed in this study is potentially useful as a local delivery system for CDA and could be used not only in surgery but also in dental and clinical applications.
Publisher: Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Faculty of Pharmacy
Date: 2021
Publisher: Elsevier BV
Date: 09-2013
DOI: 10.1016/J.BBAGEN.2012.12.018
Abstract: Organic electrochemical transistors (OECTs), which are becoming more and more promising devices for applications in bioelectronics and nanomedicine, are proposed here as ideally suitable for sensing and real time monitoring of liposome-based structures. This is quite relevant since, currently, the techniques used to investigate liposomal structures, their stability in different environments as well as drug loading and delivery mechanisms, operate basically off-line and/or with pre-prepared s ling. OECTs, based on the PEDOT:PSS conductive polymer, have been employed as sensors of liposome-based nanoparticles in electrolyte solutions to assess sensitivity and monitoring capabilities based on ion-to-electron lified transduction. We demonstrate that OECTs are very efficient, reliable and sensitive devices for detecting liposome-based nanoparticles on a wide dynamic range down to 10(-5)mg/ml (with a lowest detection limit, assessed in real-time monitoring, of 10(-7)mg/ml), thus matching the needs of typical drug loading/drug delivery conditions. They are hence particularly well suited for real-time monitoring of liposomes in solution. Furthermore, OECTs are shown to sense and discriminate successive injection of different liposomes, so that they could be good candidates in quality-control assays or in the pharmaceutical industry. Drug loading and delivery by liposome-based structures is a fast growing and very promising field that will strongly benefit from real-time, highly sensitive and low cost monitoring of their dynamics in different pharma and biomedical environments, with a particular reference to the pharmaceutical and production processes, where a major issue is monitoring and measuring the formation and concentration of liposomes and the relative drug load. The demonstrated ability to sense and monitor complex bio-structures, such as liposomes, paves the way for very promising developments in biosensing and nanomedicine. This article is part of a Special Issue entitled Organic Bioelectronics-Novel Applications in Biomedicine.
Publisher: MDPI AG
Date: 04-07-2023
DOI: 10.3390/PHARMACEUTICS15071886
Abstract: Paclitaxel (PTX) and 5-fluorouracil (5-FU) are clinically relevant chemotherapeutics, but both suffer a range of biopharmaceutical challenges (e.g., either low solubility or permeability and limited controlled release from nanocarriers), which reduces their effectiveness in new medicines. Anticancer drugs have several major limitations, which include non-specificity, wide biological distribution, a short half-life, and systemic toxicity. Here, we investigate the potential of liposome-micelle-hybrid (LMH) carriers (i.e., drug-loaded micelles encapsulated within drug-loaded liposomes) to enhance the co-formulation and delivery of PTX and 5-FU, facilitating new delivery opportunities with enhanced chemotherapeutic performance. We focus on the combination of liposomes and micelles for co-delivery of PTX and 5_FU to investigate increased drug loading, improved solubility, and transport ermeability to enhance chemotherapeutic potential. Furthermore, combination chemotherapy (i.e., containing two or more drugs in a single formulation) may offer improved pharmacological performance. Compared with in idual liposome and micelle formulations, the optimized PTX-5FU-LMH carriers demonstrated increased drug loading and solubility, temperature-sensitive release, enhanced permeability in a Caco-2 cell monolayer model, and cancer cell eradication. LMH has significant potential for cancer drug delivery and as a next-generation chemotherapeutic.
Publisher: Informa UK Limited
Date: 06-11-2008
Publisher: Springer Science and Business Media LLC
Date: 25-03-2009
Publisher: MDPI AG
Date: 28-03-2023
DOI: 10.3390/JFB14040189
Abstract: Recently, there has been increasing interest in developing biocompatible inhalable nanoparticle formulations, as they have enormous potential for treating and diagnosing lung disease. In this respect, here, we have studied superparamagnetic iron-doped calcium phosphate (in the form of hydroxyapatite) nanoparticles (FeCaP NPs) which were previously proved to be excellent materials for magnetic resonance imaging, drug delivery and hyperthermia-related applications. We have established that FeCaP NPs are not cytotoxic towards human lung alveolar epithelial type 1 (AT1) cells even at high doses, thus proving their safety for inhalation administration. Then, D-mannitol spray-dried microparticles embedding FeCaP NPs have been formulated, obtaining respirable dry powders. These microparticles were designed to achieve the best aerodynamic particle size distribution which is a critical condition for successful inhalation and deposition. The nanoparticle-in-microparticle approach resulted in the protection of FeCaP NPs, allowing their release upon microparticle dissolution, with dimensions and surface charge close to the original values. This work demonstrates the use of spray drying to provide an inhalable dry powder platform for the lung delivery of safe FeCaP NPs for magnetically driven applications.
Publisher: Elsevier BV
Date: 08-2010
DOI: 10.1016/J.JCONREL.2010.05.001
Abstract: The aim of this work was to study a multi-kinetics and site-specific oral antimalaria drug delivery system (MKS_DDS), containing artesunate and clindamycin, based on the Dome Matrix module assembly technology. The MKS_DDS assembled system comprises of four modules, i.e., two controlled release (CR) modules for delivery of 160 mg of clindamycin phosphate, one immediate release module containing 50 mg of artesunate and one immediate release module containing 80 mg of clindamycin phosphate. These modules have been assembled in stacked and void configurations. The void configuration is able to float and showed gastro-retentive behavior. The MKS_DDS was investigated for its mechanical characteristics, system behavior during release, drug release rate and mechanism. A bioavailability study (dogs) showed that the clindamycin plasma curve of the MKS_DDS system exhibited a quasi constant release rate, up to 8 h. The MKS_DDS system containing clindamycin and artesunate allows the use of one tablet containing one immediate release dose of artesunate and of clindamycin and a portion of clindamycin released over a prolonged time, by exploiting the gastro-retentive properties of a floating system.
Publisher: Informa UK Limited
Date: 2018
Publisher: Springer Science and Business Media LLC
Date: 23-10-2012
Publisher: Bentham Science Publishers Ltd.
Date: 06-2005
Abstract: In recent years the fields of medicine and biology assist to an ever-growing innovation related to the development of nanotechnologies. In the pharmaceutical domain, for ex le, liposomes, polymer based micro and nanoparticles have been subjects of intense research and development during the last three decades. In this scenario metallic particles, which use was already suggested in the first half of the '80, are now experiencing a real renaissance. In the field of diagnosis, magnetic resonance imaging is one of the first and up to now the most developed application of metallic particles. But beside this application, a very new generation of biosensors based on the optical properties of colloidal gold and fluorescent nanocrystals, called quantum dots seems to be ready to be implemented in diagnosis and medical imaging. Concerning therapeutic applications, the potentialities of metal nanoparticles to help fulfilling the need of time and space controlled release of drugs has been intuited for a long time. Nowadays, magnetically guided carriers or thermal responsive matrices, in which drug release is triggered by the heating of metal nanoparticles, are effective ex les of their application in drug delivery, while more recently efforts to develop metallic nanoobjects to be used as vectors of nucleic acids for vaccination and transfection have been multiplied. In the future, one of the most interesting challenges is certainly the use of metallic nanoparticles for an innovating, effective and selective physical treatment of solid tumors via targeted intracellular hyperthermia.
Publisher: Elsevier BV
Date: 07-2012
DOI: 10.1016/J.JCONREL.2012.02.028
Abstract: The paper briefly illustrates several approaches applied in delivering particulate drugs as powders. Microparticulate drug powders are difficult to manipulate with respect to dosage form preparation, particularly when they have very small size as this leads to poor flow and packing properties. When the dosage form performance resides in the presence of in idual intact drug particles, the particle characteristics have to be retained in their original state, i.e., not altered during manufacturing and/or within the dosage form. There are several ex les of dry powder dosage forms intended for different administration routes whose performance is strictly dependent on particle characteristics. In addition, the preparation of the finished dosage form is dependent on powder properties. The paper addresses dry powder formulations with special focus on oral powders mainly for elderly people or children, nasal powders and inhalation dry powders. These dosage forms are very attractive for both researchers and companies. Their formulation requires deep investigation, mainly in order to define particle structure and performance. Indeed, this makes for a new breakthrough in pharmaceutics and may lead to innovative products.
Publisher: Informa UK Limited
Date: 19-06-2020
Publisher: Elsevier BV
Date: 10-2006
DOI: 10.1016/J.IJPHARM.2006.06.036
Abstract: In this work the production of auto-assembled nanoparticles obtained by the mixing of chitosan and lecithin is presented. The size and surface charge of the nanoparticles were studied as function of the weight ratio between components, the viscosity of the polysaccharide and the pH of the colloidal suspension. In order to elucidate the structure of nanoparticles, micro-FT-IR and elastic neutron scattering experiments have been performed. Results evidenced a strong electrostatic interaction between components and a structure that is neither that of homogeneous spheres nor of coated unilamellar vesicles. Preliminary encapsulation experiments with progesterone, as model lipophilic drug, showed good encapsulation efficiencies.
Publisher: CRC Press
Date: 19-04-2008
DOI: 10.1201/B15115-33
Publisher: Elsevier BV
Date: 2017
DOI: 10.1016/J.IJPHARM.2016.12.002
Abstract: Sodium hyaluronate (HYA) warrants attention as a material for inhalation due to its (i) therapeutic potential, (ii) utility as a formulation excipient or drug carrier, and (iii) ability to target lung inflammation and cancer. This study aimed to overcome formulation and manufacturing impediments to engineer biocompatible spray-dried HYA powders for inhalation. Novel methodology was developed to produce HYA microparticles by spray drying. Different types of surfactant were included in the formulation to improve powder respirability, which was evaluated in vitro using cascade impactors. The in idual formulation components and formulated products were evaluated for their biocompatibility with A549 respiratory epithelial cells. The inclusion of stearyl surfactants, 5% w/v, produced the most respirable HYA-powders FPF 59.0-66.3%. A trend to marginally higher respirability was observed for powders containing stearylamine>stearyl alcohol>cetostearyl alcohol. Pure HYA was biocompatible with A549 cells at all concentrations measured, but the biocompatibility of the stearyl surfactants (based on lethal concentration 50% LC
Publisher: Elsevier BV
Date: 02-2010
DOI: 10.1016/J.EJPB.2009.11.015
Abstract: Soft agglomerates containing pantoprazole-loaded microparticles were developed with the aim of prompt delivery of gastro-resistant particles. The objective was to evaluate the relative bioavailability in dogs after the oral administration of soft agglomerates. Gastro-resistant pantoprazole-loaded microparticles prepared by spray drying were mixed with mannitol/lecithin spray-dried powder and agglomerated by vibration. One single oral dose (40mg) was administered to dogs. Each dog received either a reference tablet or hard gelatin capsules containing the agglomerates. The plasma profiles were evaluated by non-compartmental and compartmental approaches, and the pharmacokinetic parameters were determined. The agglomerates presented 100% of drug particle loading and a production yield of 80.5%. The amount of drug absorbed after oral dosing was similar after reference or agglomerate administration, leading to a relative bioavailability of 108%. The absorption lag-time was significantly reduced after agglomerate administration (from 135.5+/-50.6 to 15.0+/-2.5min). The agglomerated gastro-resistant pantoprazole-loaded microparticles reduced time to peak plasma. The agglomerates were equivalent to the reference tablets in terms of extent but not in terms of rate of absorption, showing that this formulation is an alternative to single-unit oral dosing with enteric coating and with the advantage of reducing time to effect.
Publisher: MDPI AG
Date: 04-02-2019
DOI: 10.20944/PREPRINTS201902.0034.V1
Abstract: Drug delivery to the brain represents a challenge especially in the therapy of central nervous system malignancies. Simvastatin (SVT), as other statins, has shown potential anticancer properties that are difficult to exploit in the CNS. In the present work the physico-chemical, mucoadhesive and permeability enhancing properties of simvastatin-loaded poly-& epsilon -caprolactone nanocapsules coated with chitosan for nose-to-brain administration were investigated. Lipid-core nanocapsules coated with different molecular weight (MW) chitosans (LNCchit) prepared by a novel one-pot technique were characterized for particle size, surface charge, particle number density, morphology, drug encapsulation efficiency, interaction between surface nanocapsules with mucin, drug release and permeability across two nasal mucosa models. Results show that all formulations present adequate particle size (below 220 nm), positive surface charge, narrow droplet size distribution (PDI& .2) and high encapsulation efficiency. Nanocapsules presented controlled drug release and mucoadhesive properties dependent on the MW of the coating chitosan. The results of permeation across RPMI 2650 human nasal cell line evidenced that LNCchit increased the permeation of SVT. In particular, the amount of SVT permeated after 4h for nanocapsules coated with low MW chitosan, high MW chitosan and control SVT was 13.91 & lusmn 0.78 & micro g, 9.15 & lusmn 1.23 & micro g and 1.42 & lusmn 0.21 & micro g respectively. These results were confirmed by the SVT ex vivo permeation across rabbit nasal mucosa. This study highlighted the suitability of LNCchit as promising strategy for the administration of simvastatin for a nose-to-brain approach for the therapy of brain tumors.
Start Date: 2021
End Date: 2025
Funder: European Commission
View Funded ActivityStart Date: 2014
End Date: 2018
Funder: Conselho Nacional de Desenvolvimento Científico e Tecnológico
View Funded ActivityStart Date: 2020
End Date: 2025
Funder: Associazione Italiana per la Ricerca sul Cancro
View Funded ActivityStart Date: 2007
End Date: 2009
Funder: Ministero dell’Istruzione, dell’Università e della Ricerca
View Funded Activity