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|Title:||Factors affecting trans-scleral transport of poly (butadiene-b-ethylene oxide) polymersomes||Authors:||Anita, Vincent||Keywords:||Engineering::Materials||Issue Date:||2019||Publisher:||Nanyang Technological University||Source:||Anita, V. (2019). Factors affecting trans-scleral transport of poly (butadiene-b-ethylene oxide) polymersomes. Master's thesis, Nanyang Technological University, Singapore.||Abstract:||Polymersomes are synthetic analogues of liposomes formed by the self-assembly of amphiphilic block copolymers as a result of hydrophobic-hydrophilic interactions with the surrounding solvent. These particles retain the drug loading versatility of liposomes while exhibiting enhanced membrane toughness and reduced permeability. As a relatively ‘young’ nanoparticle system, most work in the field of polymersomes focus on designing unique polymersome assemblies via synthesis of new polymers, new formulation techniques, particle functionalization etc. There is then a need to develop polymersome technology towards practical applications. In this light, this research work examines the suitability of polymersomes for ocular drug delivery via periocular route of drug administration. Periocular drug delivery presents an alternative treatment strategy for posterior segment eye disease (PSEDs) by administering drugs into the periocular space surrounding the eye orbit; the drugs then diffuse from this space across the sclera and choroid into the posterior segment of the eye, allowing for improved bioavailability and therapeutic effect. Drug loaded polymersomes could further enhance this treatment strategy by forming periocular or intrascleral drug depots capable of releasing a sustained dose of drug over extended time periods. In order to study the potential of polymersomes for periocular drug delivery via the formation of intrascleral drug depots, poly (butadiene – b- ethylene oxide) polymersomes with varying particle properties (hydrodynamic size, bilayer bending rigidity, surface charge and hydrophilicity) were formulated. All formulations were meticulously characterized in order to understand the effect of polymersome properties on trans-scleral transport behaviour as observed by ex-vivo passive transport experiments across porcine sclera. Polymersomes were found to form periocular depots in the case of most formulations with several formulations forming intrascleral depots, thus proving their viability as nanoparticles for periocular drug delivery. Further, the observed trans-scleral transport behaviours of the different polymersome formulations were found to be affected by particle properties such as hydrodynamic size, bilayer bending rigidity, surface charge and hydrophilicity. In general, small hydrophilic polymersomes with flexible bilayers and low negative surface charge were found to have maximum permeation into the sclera. In conclusion, this research study has proven the ability of poly (butadiene – b – ethylene oxide) polymersomes to form periocular and intrascleral depots which indicates the possibility of using the nanoparticle system for periocular drug delivery. Future work focused on optimizing drug loading and release of these particles would determine the eventual viability of polymersomes for periocular drug delivery.||URI:||https://hdl.handle.net/10356/137571||Rights:||This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).||Fulltext Permission:||open||Fulltext Availability:||With Fulltext|
|Appears in Collections:||MSE Theses|
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