ORCID Profile
0000-0003-4910-0005
Current Organisation
The University of Auckland
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Publisher: Informa UK Limited
Date: 17-02-2021
DOI: 10.1111/CXO.13100
Abstract: The monitoring and controlling of pH is important when preparing solutions for ophthalmic administration. In the case of povidone-iodine, dilution in an appropriate buffer is needed to improve its ophthalmic safety. Povidone-iodine is a broad-spectrum antiseptic agent that is commonly used in ophthalmic applications due to its cost-effectiveness and accessibility. However, native povidone-iodine has a pH of about 4.0 and is known to irritate the ocular surface. This study assessed whether adjusting povidone-iodine formulation pH would influence its One per cent w/v povidone-iodine was diluted in normal saline, or 0.1-mol/l citrate or phosphate buffers to yield solutions with a pH ranging from 4.0 to 7.0. Ocular irritancy was evaluated using the bovine cornea opacity and permeability assay. Antibacterial efficacy was assessed by evaluating povidone-iodine minimum inhibitory concentration and minimum bactericidal concentration at varied pH. Storage stability of the preparations was determined over 30-days at room temperature (20-25°C). Combining povidone-iodine with phosphate buffer notably decreased ocular irritancy of the antiseptic. Surprisingly, combining povidone-iodine with citrate buffer potentiated irritant effects of the preparation. Antibacterial efficacy of povidone-iodine was reduced when formulation pH was increased from 4.0 to 7.0, although its general activity was retained. Finally, povidone-iodine remained stable in both normal saline and phosphate buffer over 30-days. Ophthalmic application of povidone-iodine can be optimised by adjusting the pH of the formulation to 7.0 using phosphate buffer, reducing irritancy while maintaining adequate antibacterial efficacy and storage stability.
Publisher: Springer Science and Business Media LLC
Date: 12-12-2017
DOI: 10.1038/S41598-017-14981-X
Abstract: Physicochemical properties of nanoparticles, such as size, shape, surface charge, density, and porosity play a central role in biological interactions and hence accurate determination of these characteristics is of utmost importance. Here we propose tunable resistive pulse sensing for simultaneous size and surface charge measurements on a particle-by-particle basis, enabling the analysis of a wide spectrum of nanoparticles and their mixtures. Existing methodologies for measuring zeta potential of nanoparticles using resistive pulse sensing are significantly improved by including convection into the theoretical model. The efficacy of this methodology is demonstrated for a range of biological case studies, including measurements of mixed anionic, cationic liposomes, extracellular vesicles in plasma, and in situ time study of DNA immobilisation on the surface of magnetic nanoparticles. The high-resolution single particle size and zeta potential characterisation will provide a better understanding of nano-bio interactions, positively impacting nanomedicine development and their regulatory approval.
Publisher: Wiley
Date: 19-07-2021
DOI: 10.1002/JPPR.1750
Abstract: Baclofen is prescribed for both adults and children as a muscle relaxant, but no data exists to support an appropriate lower‐dose extemporaneously compounded oral liquid suitable for young children in New Zealand. This study aimed to determine the stability of 1 mg/mL baclofen oral suspension over 30 days. Baclofen suspensions were compounded ( n = 6 per formulation) using suspending vehicles Ora‐Blend ® (OB) or Ora‐Blend sugar‐free ® (OB SF) and stored at either 25°C/60% relative humidity or 2–8°C for 30 days. Organoleptic properties, sedimentation volume ratio, ease of redispersion, pH and baclofen content were determined. Formulations required 2–3 inversions to redisperse at each time point. A colour change was observed from day 14 in the OB suspensions stored at both temperatures, likely due to the Maillard reaction, whereas no colour change was observed in any OB SF suspensions. The pH of all formulations remained between 4.5 and 4.6. Both OB and OB SF suspensions retained % of the initial baclofen concentration over 30 days. Although baclofen 1 mg/mL suspensions prepared in both OB and OB SF retained sufficient baclofen to be considered chemically stable in both storage conditions over the study period, OB SF is recommended as a preferred vehicle over OB formulations due to the colour change observed.
Publisher: Springer Science and Business Media LLC
Date: 12-12-2022
Publisher: Elsevier
Date: 2018
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.EJPB.2019.01.014
Abstract: The intravitreal route faces many challenges in rapidly and effectively reaching posterior eye pathology, with administered therapeutics experiencing non-specific distribution around and premature clearance from ocular tissues. Nanobubbles and ultrasound may improve outcomes of intravitreally administered drugs by influencing the directionality of drug-containing particle migration. In this study, we assessed the impact of trans-scleral or corneal ultrasound application on the distribution of intravitreally-injected nanobubbles. Rhodamine-tagged gas entrapped nanobubble formulations were prepared and injected into ex vivo bovine and porcine eyes and subjected to ultrasound (1 MHz, 0-2.5 W/cm
Publisher: S. Karger AG
Date: 22-11-2018
DOI: 10.1159/000493488
Abstract: The use of corneal tissue for ex vivo therapeutic evaluations is limited due to its rapid loss of viability after excision. Optimization of storage conditions may allow prolonged retention of physical tissue properties. In this study, we evaluated how storage in optimized organ culture (OC) medium at 37°C or phosphate-buffered saline (PBS) at 2–8°C impacted physical properties of bovine corneas. Tissue hydration, permeability and histology were monitored at baseline and following 1, 4 and 7 days of storage. Corneas stored in OC demonstrated significantly higher hydration and permeability when compared to those stored in PBS. Histology revealed that storage in OC consistently caused detachment of the epithelial layer by day 4 of storage, whereas both storage conditions caused a significant increase in stromal thickness and tissue vacuolation. This study highlights the limitations of currently available corneal tissue storage approaches for ex vivo drug permeation studies.
Publisher: Elsevier BV
Date: 05-2020
Publisher: Public Library of Science (PLoS)
Date: 25-05-2017
Publisher: Informa UK Limited
Date: 03-09-2017
DOI: 10.1080/10837450.2017.1371191
Abstract: This study reports on the impact of cyclodextrin addition on the phase behavior of microemulsion systems. Three distinct oil-in-water microemulsions were formulated and subjected to increasing concentrations of various cyclodextrins. The prepared formulations underwent visual, textural and microscopic characterization followed by the evaluation of their in vitro drug release and ex vivo tissue retention behavior. Combining microemulsions with cyclodextrins resulted in either phase separation or transition into a liquid crystalline state depending on the concentration and type of cyclodextrin utilized. Formulations combined with α-cyclodextrin consistently demonstrated transition into a liquid crystalline state as confirmed by polarized light and cryo-scanning electron microscopy. In these cases, cyclodextrin addition was also positively correlated with an increase in formulation hardness, adhesiveness and turbidity. Release and clearance studies revealed that drug diffusion from the microemulsions could be slowed and tissue retention prolonged by increasing the cyclodextrin content. These findings pave the way for the development of novel cyclodextrin-microemulsion-based liquid crystalline formulations in a variety of sustained drug delivery applications.
Publisher: Elsevier BV
Date: 02-2015
DOI: 10.1016/J.IJPHARM.2015.01.003
Abstract: Resveratrol, a naturally occurring polyphenol and phytoalexin, has received significant attention in recent years due to its vast therapeutic effects including anticancer, antioxidant and anti-inflammatory effects. However, poor pharmacokinetic properties such as low aqueous solubility, low photostability and extensive first pass metabolism result in poor bioavailability, hindering its immense potential. Conventional dosage forms such as dry powder capsules and injections have met with limited success, demonstrating challenges faced in developing an effective formulation. Recently, nanotechnology-based formulations (nanoformulations) are being looked upon as a novel method for improving the pharmacokinetic properties, as well as enhancing targetability and bioavailability of resveratrol. This review outlines the therapeutic potential of resveratrol, explores its mechanisms of action and pharmacokinetic limitations, and discusses the success and challenges of resveratrol-encapsulated nanoparticles in the last decade. Potential techniques to improve encapsulation of the drug within nanoparticles, thereby enhancing its clinical potential are highlighted.
Publisher: Elsevier BV
Date: 03-2020
DOI: 10.1016/J.EJPB.2020.01.008
Abstract: Artificial vitreous humor holds immense potential for use in in vitro intravitreal drug delivery assays. In this study, we investigated rheological properties and drug or nanoparticle migration in hyaluronic acid (HA) - agar based hydrogels and compared these characteristics with bovine vitreous humor. Gel compositions identified in literature containing HA (0.7-5.0 mg/ml) and agar (0.95-4.0 mg/ml) were classified as either high (VH), medium (VM) or low (VL) polymer load. Viscoelastic behavior was evaluated using oscillatory rheology, and migration of differently sized and charged polystyrene nanoparticles (NPs) through the different gels was determined via multiple particle tracking. Comparable rheological behaviour was observed between VL and bovine vitreous. Tracking evaluations revealed that increasing particle size and gel viscosity slowed NP migration. Additionally, 100 nm anionic NPs migrated slower than neutral NPs in VL and VM, while cationic NPs were immobile in all gels. Finally, distribution and clearance of sodium fluorescein was used to model drug mobility through the gels using a custom-built eye model. Flow and angular movement only influenced drug migration in VL and VM, but not VH. Finally, VL and VM demonstrated to have the most similar sodium fluorescein clearance to that of bovine vitreous humor. Together, these evaluations demonstrate that low viscosity HA-agar gels can be used to approximate nanoparticle and drug migration through biological vitreous humor.
Publisher: Elsevier BV
Date: 2016
DOI: 10.1016/J.JCIS.2015.10.022
Abstract: Despite the known anticancer potential of resveratrol, its clinical applications are often hindered by physicochemical limitations such as poor solubility and stability. The encapsulation of resveratrol in formulations such as polymeric nanoparticles and liposomes has shown limited success. This study aimed to develop and optimize a novel drug carrier by co-encapsulating pristine resveratrol alongside cyclodextrin-resveratrol inclusion complexes in the lipophilic and hydrophilic compartments of liposomes, respectively by using a novel dual carrier approach. The particle size, polydispersity index and zeta potential of the final formulation were 131±1.30nm, 0.089±0.005 and -2.64±0.51mV, respectively. Compared to free resveratrol and conventional liposomal formulations with drug release profile of 40-60%, our novel nanoformulations showed complete (100%) drug release in 24h. The formulation was stable for 14days at 4°C. We also studied the in vitro cytotoxicity of resveratrol encapsulated liposomes in HT-29 colon cancer cell lines. The cytotoxicity profile of our liposomes was observed to be dose dependent and enhanced in comparison to free resveratrol (in DMSO). Our study demonstrates that co-encapsulation of pristine resveratrol along with its cyclodextrin complex in liposomal formulations is a plausible option for the enhanced delivery of the hydrophobic chemotherapeutic agent.
Publisher: Springer International Publishing
Date: 2018
Publisher: Informa Healthcare
Date: 14-06-2014
DOI: 10.1517/17425247.2014.927864
Abstract: With the ever-increasing global burden of retinal disease, there is an urgent need to vastly improve formulation strategies that enhance posterior eye delivery of therapeutics. Despite intravitreal administration having demonstrated notable superiority over other routes in enhancing retinal drug availability, there still exist various significant physical/biochemical barriers preventing optimal drug delivery into the retina. A further complication lies with an inability to reliably translate laboratory-based retinal models into a clinical setting. Several formulation approaches have recently been evaluated to improve intravitreal therapeutic outcomes, and our aim in this review is to highlight strategies that hold the most promise. We discuss the complex barriers faced by the intravitreal route and examine how formulation strategies including implants, nanoparticulate carriers, viral vectors and sonotherapy have been utilized to attain both sustained delivery and enhanced penetration through to the retina. We conclude by highlighting the advances and limitations of current in vitro, ex vivo and in vivo retinal models in use by researchers globally. Various nanoparticle compositions have demonstrated the ability to overcome the retinal barriers successfully however, their utility is limited to the laboratory setting. Optimization of these formulations and the development of more robust experimental retinal models are necessary to translate success in the laboratory into clinically efficacious outcomes.
Publisher: Elsevier BV
Date: 10-2017
DOI: 10.1016/J.EJPB.2017.06.009
Abstract: Intravitreal injection is the most common administration route for the treatment of retinal diseases. However, the vitreous and some of the retinal layers themselves act as significant barriers to efficient delivery of drugs administered intravitreally. This study aimed to improve the diffusive mobility of nanoparticles (NPs) in the vitreous and enhance their permeation across the retina after intravitreal injection by application of ultrasound (US). Ex vivo posterior bovine eye cups were used and the vitreous was either left intact or removed gently from the neural retina. Hyaluronic acid coated human serum albumin NPs were administered into the eye cups and continuous US with a frequency of 1MHz, an intensity of 0.5W/cm
Publisher: Elsevier BV
Date: 02-2018
Publisher: Elsevier BV
Date: 04-2021
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.DRUDIS.2019.03.023
Abstract: The periocular space is a promising alternative route for the delivery of drugs to the posterior eye segment, especially when treating conditions in the outer ocular layers. In this review, we discuss the different periocular routes as well as the physiological barriers and elimination mechanisms limiting drug bioavailability at the back of the eye. We then highlight various types of depot formulations, including particulate delivery systems, semisolid formulations, and implants, used to increase the contact time with the ocular tissues. With the additional advantage of sustaining drug release, such depot formulations could enhance periocular drug delivery to the posterior eye segment.
Publisher: Wiley
Date: 22-05-2015
Publisher: S. Karger AG
Date: 04-11-2017
DOI: 10.1159/000481691
Abstract: The use of sunscreen products is widely promoted by schools, government agencies, and health-related organizations to minimize sunburn and skin damage. In this study, we developed stable solid lipid nanoparticles (SLNs) containing the chemical UV filter octyl methoxycinnamate (OMC). In parallel, we produced similar stable SLNs in which 20% of the OMC content was replaced by the botanical urucum oil. When these SLNs were applied to the skin of human volunteers, no changes in fluorescence lifetimes or redox ratios of the endogenous skin fluorophores were seen, suggesting that the formulations did not induce toxic responses in the skin. Ex vivo (skin diffusion) tests showed no significant penetration. In vitro studies showed that when 20% of the OMC was replaced by urucum oil, there was no reduction in skin protection factor (SPF), suggesting that a decrease in the amount of chemical filter may be a viable alternative for an effective sunscreen, in combination with an antioxidant-rich vegetable oil, such as urucum. There is a strong trend towards increasing safety of sun protection products through reduction in the use of chemical UV filters. This work supports this approach by producing formulations with lower concentrations of OMC, while maintaining the SPF. Further investigations of SPF in vivo are needed to assess the suitability of these formulations for human use.
Publisher: Elsevier BV
Date: 07-2020
Publisher: Informa UK Limited
Date: 11-2019
DOI: 10.1111/CXO.12899
Abstract: Povidone-iodine is used as a cost-effective broad-spectrum antiseptic in the prophylaxis and treatment of certain ocular infections. In this study, the stability, ophthalmic irritation potential and antibacterial efficacy of an extemporaneous povidone-iodine preparation was determined using established ex vivo and in vitro assays. Extemporaneous iodine was prepared by simple dilution in normal saline. Preparation stability was evaluated by monitoring concentration and pH. Ocular safety was determined using the bovine cornea opacity and permeability assay. Efficacy was assessed by determining the minimum inhibitory and minimum bactericidal concentration of the preparation on Staphylococcus aureus and Pseudomonas aeruginosa. Diluted povidone-iodine maintained its stability over the 28-day evaluation. The formulation caused mild ocular irritation at the lowest prepared concentration (0.5 per cent w/v), with irritation noticeably increased at higher concentrations. The preparation showed minimum bactericidal and inhibitory concentrations of 0.078 and 0.3 per cent w/v on S. aureus and P. aeruginosa, respectively. This study confirms the stability and broad-spectrum antibacterial efficacy of povidone-iodine, while addressing the ocular irritation potential of this chemical.
Publisher: MDPI AG
Date: 22-10-2020
DOI: 10.3390/GELS6040037
Abstract: Collagen is the most abundant protein in mammals and possesses high biocompatibility and low antigenicity. These biological properties render it one of the most useful biomaterials for medical applications. This study investigated the mechanical and physical characteristics of collagen hydrogels cross-linked with different ratios of polyvinylpyrrolidone capped zinc oxide nanoparticles (ZPVP). Fourier transform infrared spectroscopy indicated molecular interactions between collagen fibers and ZPVP. Texture analysis revealed a significant increase in gel hardness, adhesiveness, and viscosity after cross-linking with ZPVP. Rheological measurements showed that as the ratio of ZPVP increased, stronger hydrogels were formed which in turn resulted in more sustained release of the model drug, dexamethasone sodium phosphate. We can therefore conclude that the mechanical properties of collagen hydrogels can be modified by controlling the ratio of ZPVP used for cross-linking, offering the potential to develop biocompatible sustained release drug delivery systems.
Publisher: Wiley
Date: 05-01-2021
DOI: 10.1002/CBIN.11477
No related grants have been discovered for Sachin Thakur.