AbstractThis thesis involves the application of different amphiphilic copolymers as self-assembling nanoparticulate drug delivery systems such as micelles and polymersomes. The first chapter starts with the introduction to nanoparticulate drug delivery systems and the significance of liposomes to nanoparticulate drug delivery research. It describes the advantages of polymeric systems as future contenders in the preparation of nanoparticles. Later, different types of self-assembling copolymers and the methods of preparation of different nanoparticles are discussed. The chapter concludes with the recent applications of polymeric micelles and polymersomes in several areas of drug delivery and diagnostics.
The second chapter presents the comparison of liposomes made from egg phosphatidylcholine, cholesterol and PEG conjugates (Mn 500 and Mn 2000) with polymersomes made from random copolymers having the same composition to that of the liposomes. The polymersomes were neutral in charge due to the absence of zwitterionic choline head groups as compared to liposomes. They were found to be smaller in size than liposomes when prepared by the reverse phase evaporation method. The comparison of polymersomes to liposomes revealed enhanced cellular uptake and good stability upon storage for the polymersome preparations.
The third chapter of this research thesis focuses on the application of polymeric micelles for triggered drug delivery combined with real time monitoring of drug release using FRET. The micelles were prepared from amphiphilic random copolymers comprising of a decyl chain group and PEG (Mn 500) and encapsulated a FRET pair of bodipy and spiropyran compounds. The spiropyran moiety is capable of ring transformation to its merocyanine counterpart upon triggering by UV light. This transformation leads to the release of some of the micellar contents to the surrounding media while concomitantly displaying a molecular communication with the bodipy moiety remaining within the micelle. The in-vitro release of merocyanine and FRET efficiency between bodipy and 5 merocyanine in HeLa cells was confirmed. Validation of real time quantification of spiropyran conjugated API release through bodipy fluorescence was also demonstrated.
Finally, the fourth chapter establishes the application of amphiphilic copolymer polymersomes for enhanced anticancer therapy. Three anticancer drugs namely, Dox, 5- FU and Leucovorin calcium were encapsulated into polymersomes and observed for invivo anti-tumour effects in pancreatic BxPC-3 ectopic xenograft mouse model after intratumoral and intravenous injections. Polymersomes encapsulated with the anticancer agents displayed an enhanced tumour reduction and less peripheral toxicity as compared to combination free drug solution at the same concentration. In conclusion, the work presented within this thesis highlights the important role of amphiphilic polymers within drug delivery.
|Date of Award||May 2018|
|Sponsors||Vice Chancellors Research Scholarship|
|Supervisor||John Callan (Supervisor), Bridgeen Callan (Supervisor) & Anthony Mc Hale (Supervisor)|
- Drug Delivery
- Combination Chemotherapy