In-vitro drug release from biodegradable matrices : analysis, modeling and application in vascular stents.
Lao, Luciana Lisa.
Date of Issue2008
School of Materials Science and Engineering
Our laboratory has been developing a completely biodegradable coronary stent which is made of bi-Iayers of biodegradable polyesters. This thesis presents the investigations carried out to exploit the drug delivery potential of such a polymeric stent. The main objective of this work was to understand and control the release of anti-proliferative drugs from biodegradable polymer films. Such understanding enabled us to explore further the effect of the controlled release of anti-proliferative drug on smooth muscle cell viability. In the bilayer films, an anti-proliferative drug such as paclitaxel is loaded on to the "top" layer that contacts the blood vessel endothelium, while an anti-thrombotic drug such as heparin may be incorporated into the "bottom" of lumen-facing side. Paclitaxel release from P(DL)LGA layer consists of three distinct stages: (i) extremely slow initial release, (ii) accelerated degradative, relaxation-induced release, and (iii) diffusional release. The effect of additives that accelerate release of paclitaxel from P(DL)LGA was studied using in vitro methods. Addition of 10 wt% PEG into P(DL)LGA reduced the induction period by half while replacing P(DL)LGA with PCL resulted in an initial burst followed by a rapid diffusion.