Chemical and Biomolecular Engineering - Theses
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ItemTunable polymer capsules for therapeutic delivery applications( 2013)The area of therapeutic drug and gene delivery has made rapid progress over the last two decades. This interest in the development of drug delivery systems is aimed at protecting the body from the non-specific side effects of drugs and biomolecules; protecting therapeutic compounds from premature degradation and directing them specifically to target sites; and having tunable carrier degradation and cargo release to optimise the therapeutic efficacy. Of the drug delivery systems studied, the Layer-by-Layer (LbL) approach for the assembly of polymer multilayer films and capsules is of particular interest because it is a facile and highly versatile assembly technique that allows for specific properties to be tailored into the assembled materials to fulfill various criteria needed for the successful bioapplication of these systems. This thesis focuses on the development of a biologically compatible polymer capsule system based on the LbL technique and the incorporation of chemical and physical approaches to achieve stable cross-linked capsules, cargo loading and controlled release. Specifically, the work aims to (i) study the film build up and characteristics of cross-linked polymer films and capsules; (ii) develop stable polymer capsules capable of loading a cargo; (iii) demonstrate a modular approach in achieving tunable capsule degradation and cargo release; and (iv) provide some insight into the behaviour of these capsules in in vitro cell studies. This is demonstrated through the fundamental studies of the assembly of a low-fouling poly(N-vinyl pyrrolidone) (PVPON) capsule which uses a cross-linker in film stabilisation. The cross-linker has a reducible disulphide bond that endows the capsules with stimuli-responsive degradable properties. The optimised capsule system is loaded with a model plasmid DNA and used to demonstrate tunable carrier degradation and cargo release behaviour, through the use of the cross-linkers, in simulated cellular reducing environment. The study is extended to the assembly of hybrid systems, which is based on incorporating a charge-shifting polymer poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) and a block copolymer poly(2-(methacryloyloxy)ethyl-phosphorylcholine)-b-poly(2-(diisopropyl-amino)ethyl methacrylate) (PMPC-PDPA), into films and capsules. These hybrid systems are investigated for their properties. Finally, these different capsule systems are investigated for their interaction and internalisation behaviour in in vitro cell studies. The preliminary results offer some insight into the potential use of these highly engineered drug delivery carriers in biomedical applications.