Controlled release and targeted drug delivery using polyelectrolyte microcapsules.
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Polyelectrolyte microcapsules were first established in 1998 as a potential drug delivery vehicle. Despite being well-established, microcapsules have not yet been thoroughly considered as a viable means of targeted drug delivery. This is largely due to the fact that microcapsules are inherently prone to unspecific binding to cells and proteins. Targeted delivery of drugs to specific diseased sites in the body is an area of research that has attracted many studies, particularly in drug deliveries that utilise microparticles. By achieving targeted delivery of a drug, one can increase the efficacy of the treatment, thus, reducing unwanted side effects. This thesis investigates methods which can modify these microcapsules in order to fine tune the release of the encapsulated drug as well as site-specific delivery of these vesicles i.e. obtain spatiotemporal control. To this end, biodegradable microcapsules of varying constituents are manufactured and their biodegradability is indirectly measured through quantification of the release of an encapsulated fluorescent protein (Rhodamine B-BSA). Fluorometry analysis of the supernatants of these microcapsule suspensions indicated that microcapsules synthesised from poly-L-arginine and poly-L-glutamic acid have the ability to encapsulate bovine serum albumin (BSA) with a high encapsulation efficiency (79.7%). Furthermore, they are able to produce a sustained release of BSA over a period of 5 Days. To complement this controlled-release study, an investigation into self-degradable microcapsules was undertaken. To achieve this, proteinase was encapsulated in both biodegradable and non-biodegradable microcapsules of different thickness. Analysis of the protein release over a period of 24 hours revealed that the release profiles of these microcapsules can be successfully controlled. Biodegradable microcapsules released 87% more protein than their non-biodegradable counterpart after 2 hours of incubation in deionised water. This provides conclusive evidence that the biodegradable microcapsules were, indeed, self-degradable. The latter part of this thesis focuses on achieving specific and exclusive targeted delivery using polyelectrolyte microcapsules, with respect to protein substrates. This is accomplished by creating an antibody-functionalised poly(ethylene glycol) (PEG) assembly within the microcapsule structure. Site-specific adsorption of these microcapsules is tested using protein micropatterns. Results obtained from adsorption assays using anti-collagen type IV-functionalised microcapsules show a 600-fold increase in binding to collagen type IV islands, compared to control proteins (fibronectin and BSA). This proves that significant adsorption was achieved on the target protein, with unspecific adsorptions being heavily suppressed on control proteins. Furthermore, similar results were found when microcapsules were functionalised with anti-fibronectin and exposed to fibronectin, highlighting the versatility of this type of biofunctionalisation.
AuthorsDeo, Devendra Inder
- Theses