For controlled drug delivery applications, an ideal carrier system should release its drug payload only at the site where the therapeutic activity is required. One elegant strategy for site-selective release of drugs is to utilize the acidic sites in the body, for example, tumor sites and intracellular endocytic compartments. The objective of this thesis is to develop a series of new acid-cleavable polymeric nanoparticles for pH-triggered delivery oftherapeutics. Four new acid-cleavable benzaldehyde acetal crosslinkers have been designed and synthesized. They were then used in the generation of acid-labile polymeric nanoparticle drug carrier systems via various synthetic strategies and drug loading approaches for the delivery of therapeutics with different nature: (l) the coreshell poly(butyl acrylate)-g-poly(polyethylene glycol acrylate) nanoparticles, synthesized via the reversible addition-fragmentation chain transfer (RAFT)-mediated dispersion polymerization, were used for the delivery of hydrophobic drugs; (2) the core-crosslinked poly(hydroxyethyl acrylate)-b-poly(butyl acrylate) copolymer micelles, synthesized via the RAFT-mediated chain-extension polymerization, were used for the delivery of an antitumor drug, doxorubicin; (3) the poly(hydroxyethyl methacrylate) microgel particles, synthesized via the inverse-emulsion polymerization, were used for the delivery of biomacromolecular drugs. The designed physiochemical features such as the size, surface chemistry, cytotoxicity and the pH-triggered drug release properties of the developed carrier systems have been assessed. The synthesized systems offered release of the drug payload at slightly acidic conditions. The structural integrity of the polymeric carriers remained intact in the physiological, neutral pH conditions. The results support the potential value of the developed systems to be used for acidic-site delivery of therapeutics e.g. tumor sites and intracellular compartments. The content of this thesis has been published as three peer-reviewed international journal articles.
| Identifer | oai:union.ndltd.org:ADTP/258272 |
| Date | January 2007 |
| Creators | Chan, Yannie Ka Yan, Chemical Sciences & Engineering, Faculty of Engineering, UNSW |
| Publisher | Awarded by:University of New South Wales. Chemical Sciences & Engineering |
| Source Sets | Australiasian Digital Theses Program |
| Language | English |
| Detected Language | English |
| Rights | Copyright Chan Yannie Ka Yan., http://unsworks.unsw.edu.au/copyright |
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