Chemical and Biomolecular Engineering - Theses

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    Tunable polymer capsules for therapeutic delivery applications
    NG, SHER LEEN ( 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.
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    Biologically compatible thin films by click chemistry
    Kinnane, Cameron Rhys ( 2010)
    The assembly of materials by the Layer-by-Layer (LbL) method provides a versatile and flexible method of assembling nanoscale structures with tailored composition, thickness, size, shape and functionality. Many conventional methods of assembling materials such as thin films and hollow polymer capsules fall short in achieving versatile, covalently bound multilayers. Combining click chemistry, a highly efficient and specific set of reactions, with the established LbL technique provides a number of advantages for the preparation of thin films and hollow polymer capsules. The click-LbL approach permits the production of stable, tailored and functionalisable materials through the modular assembly of a variety of building blocks. This thesis focuses on developing biologically compatible thin films and capsules by the click- LbL technique. Specifically, this work aims to: (i) investigate the fundamental factors controlling the growth and characteristics of click-LbL films; (ii) develop stable, biocompatible films; (iii) demonstrate that click chemistry is a facile and flexible means of functionalising multilayer films; and (iv) demonstrate that click-LbL films are capable of performing specific roles within biological systems. This will be demonstrated through a fundamental study on the assembly of thin films and capsules through assembly of alkyne- and azide-functional poly(acrylic acid) building blocks by the click-LbL technique. The technique is then extended to the assembly of covalently bonded films comprised solely of poly(ethylene glycol) (PEG) acrylates that limit the adsorption of serum proteins. By functionalising click-LbL films of PEG with a cell adhesion promoting peptide, these films then demonstrate the specific adhesion and growth of cells onto a surface. Multilayer films are also assembled using temperature-responsive PEG methacrylate copolymers and their ability to resist the adsorption of proteins from human serum is tested. Hollow capsules comprised of poly(N-vinyl pyrrolidone), with demonstrated low-cytotoxicity, are then produced by multilayer assembly onto colloidal silica. These capsules are covalently stabilised through a click-functionalised cross-linking agent, which can be cleaved under reducing conditions, to deconstruct capsules. The demonstrated properties of click-LbL films and capsules presented herein, offer potential for chemical engineering, pharmaceutical and in particular, biological applications.