Development of a Novel Drug Delivery System Based on Conducting Polymers

Abstract

Controlled release systems offer advantages over conventional therapies by maintaining drug concentrations at therapeutically desired levels whilst simultaneously improving compliance. Intrinsically Conducting Polymers (ICP) are organic materials that have electrical, magnetic and optical properties usually associated with metals, whilst retaining the advantageous mechanical properties and ease of processing usually associated with polymers. A novel drug delivery system, based on the ICP polypyrrole (PPy), has been developed to provide for the controlled release of risperidone. Due to the inherent properties of ICPs, electrical stimulation can be used to alter the redox state of PPy, which in turn can modify the release rate of drug. A validated, specific, stability indicating high performance liquid chromatography (HPLC) analytical method was used to quantify drug release from PPy films. PPy was selected as the platform material for drug delivery due to its inherent conductivity, ease of preparation and apparent biocompatibility. Various anionic dopants were trialled in the preparation of PPy films - p-toluene sulfonate produced the optimal formulation (PPy-pTS). PPy-pTS films were prepared containing risperidone (8.2 % w/w). Drug release profiles could be altered by applying different electrical stimulation. The rate of drug release could be increased or decreased by applying or withholding electrical stimulation. Atomic Force Microscopy was used to investigate changes in PPy film thickness when different stimuli were applied. The highest levels of drug release were observed when PPy was reduced; this was accompanied by expansion of the film. In order to be used clinically, the films must be functional over a defined shelf life. Stability studies suggested polymer morphology altered over time, accompanied by changes in risperidone release. In general, while aging slowed the rate of risperidone release from PPy films, release rates could be altered through electrical signalling in polymer films stored for up to 4 weeks at 40 °C. This project relied on the multidisciplinary collaboration of pharmaceutical scientists, chemists and clinicians. The described technology could be utilised for implantable drug delivery devices, where the dose could be adjusted by external signalling, optimising patient benefit to side effect ratios while simultaneously ensuring compliance.