Evaluation of advanced paclitaxel drug delivery implants for controlled release post-surgical treatment against glioblastoma multiforme in the brain

Abstract

This thesis presents the evaluation of three different Paclitaxel controlled release biodegradable implants based on PLGA for post-surgical implantation, fabricated in the form of Pressure-Quenched Foams, EHDA microparticles and Spray-Dried Discs. Two formulations of foams were evaluated (5% Paclitaxel-loaded PLGA85:15 foams and 10% Paclitaxel PLGA50:50 foam). In vitro cell cultures showed suppressed cell proliferation and increased apoptotic activity of release from foams vs. acute Paclitaxel exposure over 24 hours. Paclitaxel Biodistribution in brain tissue were sustained at ~3 mm over 28 days.Electrohydrodynamic microparticles achieved an in vivo release for 28 days. In an tumor-response study, the data suggests enhanced tumor suppression and significant survivability over commercial TaxolA?.The in vivo release of Sprayed Discs showed correlation to the published Wang et al (2003). The results suggest that in an in vivo environment, sustained release can be achieve for up to 42 days with a peak after 21 days.