Fabrication of drug delivery systems

The aim of the studies in this thesis was to investigate drug delivery systems using a variety of fabrication techniques that can be used for biomedical devices. This thesis was conducted in partnership with the HEARing Cooperative Research Centre (CRC) with the aim of developing drug delivery systems that can be incorporated into the cochlear implant (Cochlear Pty. Ltd is a partner of the HEARing CRC). Therefore the materials used to form the drug delivery systems and the fabrication approaches were chosen and used with the final application of the cochlear implant in mind. First, a multifunctional polypyrrole based system was developed to electrochemically deliver dexamethasone disodium phosphate (DexP) - a derivative of anti-inflammatory drug dexamethasone (Dex). Additionally this system was modified to render the surface resistance to nonspecific protein adsorption. This study investigated different conditions for the electropolymerisation of DexP doped polypyrrole (PPy/DexP) films, and their impacts on the film properties (e.g. morphology, impedance) and the electrically-stimulated drug release profiles. Poly(ethylene glycol) methyl ether thiol (PEG-SH) with different molecular weights were introduced to modify the PPy/DexP film surface and a quartz crystal microbalance (QCM) was used to study the modification of the PPy/DexP films, as well as protein interaction with PPy/DexP films before and after the PEG-SH modification. The second part of this study involved exploring the possibility to increase the loading of the anti-inflammatory drug using a hydrogel reservoir system. A multipleprinthead inkjet printer was developed to print alginate-chitosan hydrogels. The ink formulations were investigated and optimised to achieve optimum printing with alginate or chitosan, as well as the reactive printing of alginate-chitosan hydrogel with both inks. Phenol red or DexP was loaded in the alginate ink and incorporated into the printed alginate-chitosan hydrogel samples during the reactive printing, and their in vitro release profiles were studied. In the third part of this study, the application of melt extrusion printing to fabricate three-dimensional (3D) scaffolds for drug delivery was demonstrated. Polycaprolactone (PCL) was chosen for its good biocompatibility and processability. PCL-Dex material was made by mixing Dex within PCL at varying concentrations using a solvent casting method. The processability of PCL-Dex was investigated through a series of characterisation methods, including thermal gravimetric analysis, differential scanning calorimetry, and rheometry. The ability to control the release of Dex from intricately fabricated 3D scaffolds was demonstrated in vitro.