Effects of 10-hydroxycamptothecin, delivered from locally injectable poly(lactide-co-glycolide) microspheres, in a murine human oral squamous cell carcinoma regression model

This study investigated whether local delivery of 10-hydroxycamptothecin pr ovides effective inductive chemotherapy as assessed by significant tumor re duction. Established tumorigenic human oral squamous cell carcinoma cells w ere used for these experiments. The experimental groups were comprised of: control (blank (no drug) poly(lactide-co-glycolide) (PLGA) microspheres), i ntraperitoneal 10-hydroxycamptothecin delivery + blank microspheres, local bolus 10-hydroxycamptothecin + blank, microspheres, and PLGA controlled-rel ease microspheres. The 10-hydroxycamptothecin dose administered was 12 mg/k g (bolus-intraperitoneal, local) or controlled-release over 10 days. Regard less of delivery route, 10-hydroxycamptothecin significantly reduces tumor volume. However, PLGA microspheres provide significantly higher intratumor- drug concentrations (similar to 10 and 100 fold higher) relative to local b olus and intraperitoneal routes, respectively. Also, only the PLGA microsph eres significantly reduced tumor weights. Camptothecin clinical application s are limited by drug inactivation at physiological pH and the need for sus tained infusions. However; due to their acidic, camptothecin- stabilizing m icroclimate, PLGA microspheres could provide a novel delivery system for ca mptothecin-based induction chemotherapy.