Year

2010

Degree Name

Doctor of Philosophy

Department

University of Wollongong. School of Chemistry

Abstract

Controlled drug delivery has been widely researched since being introduced over 50 years ago. Systems for controlled release are important for improving the pharmacological profile of therapeutic compounds. Controlled delivery systems have been designed to give sustained and delayed release as well as for targeted delivery which minimises side effects such as toxicity, which can be associated with systemic drug delivery. Many materials have been used for controlled release, with the main focus being on polymer based systems.

Over recent years conducting polymers have been used in controlled drug release applications. These materials possess unique redox switching properties which enable ionic compounds, including drugs, to be incorporated into and released from the polymer with electrochemical stimulation. To date, the use of conducting polymers in release systems has been focussed almost solely on polypyrrole. The work in this thesis focuses on another conducting polymer, polyterthiophene, for the incorporation and release of an anionic anti-inflammatory drug, dexamethasone phosphate (Dex).

Dex was successfully incorporated into polyterthiophene as an anionic dopant during electrochemical synthesis. Due to the differing solubility of the drug and terthiophene monomer, synthesis was carried out from a mixed solvent system of water and acetonitrile. Characterisation showed that the presence of water in the monomer solution did not have a significant effect on the properties of the resulting polymer. Polymer synthesis conditions were optimised to yield reproducible polymer films which gave consistent Dex release profiles. The release of Dex was studied using arange of electrochemical stimulation protocols, with the oxidation state of the polyterthiophene found to be critical to the release observed. Polyterthiophene films were found to spontaneously reduce when immersed in electrolyte solution. Consequently, little difference in the release was observed between the unstimulated (spontaneously reduced) polymer and polyterthiophene which had been electrochemically reduced. However, the application of a constant oxidising potential was found to significantly reduce the rate of release from polyterthiophene.

Several composite structures based on polyterthiophene doped with Dex were subsequently studied to determine whether this spontaneous reduction phenomenon could be changed or prevented. Bilayer structures prepared with an inner polyterthiophene layer and outer polypyrrole layer both doped with Dex were studied. Raman characterisation showed that some reduction of the inner polyterthiophene layer did occur. However, the Dex release profiles obtained for the bilayer structures were significantly different from those obtained for polyterthiophene mono layer structures, indicating that incorporating an outer polypyrrole layer could be used to affect release from the inner polyterthiophene layer. The use of carbon-based substrates was shown to stabilise the oxidation state of polyterthiophene doped with Dex in air, however, auto-reduction still occurred upon immersion in solution. Comparative release studies carried out using polypyrrole doped with Dex gave unique release results, with a significant amount of Dex release observed when a constant highly oxidising potential was applied to the polypyrrole film.

Galvanic coupling with magnesium based alloys was shown as a means of stimulating drug release from polypyrrole and polyterthiophene/polypyrrole bilayer structures, removing the need for an external power source to stimulate release.

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