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 provides effective inductive chemotherapy as assessed by significant tumor reduction. Established tumorigenic human oral squamous cell carcinoma cells were used for these experiments. The experimental groups were comprised of: control (blank (no drug) poly(lactide-co-glycolide) (PLGA) microspheres), intraperitoneal 10-hydroxycamptothecin delivery + blank microspheres, local bolus 10-hydroxycamptothecin + blank microspheres, and PLGA controlled-release microspheres. The 10-hydroxycamptothecin dose administered was 12 mg/kg (bolus-intraperitoneal, local) or controlled-release over 10 days. Regardless of delivery route, 10-hydroxycamptothecin significantly reduces tumor volume. However, PLGA microspheres provide significantly higher intratumor-drug concentrations (approximately 10 and 100 fold higher) relative to local bolus and intraperitoneal routes, respectively. Also, only the PLGA microspheres significantly reduced tumor weights. Camptothecin clinical applications are limited by drug inactivation at physiological pH and the need for sustained infusions. However, due to their acidic, camptothecin-stabilizing microclimate, PLGA microspheres could provide a novel delivery system for camptothecin-based induction chemotherapy.
Mallery, SR; Shenderova, A; Pei, P; Begum, S; Ciminieri, JR; Wilson, RF; Casto, BC; Schuller, DE; Morse, MA
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