In vitro release behavior of paclitaxel and carboplatin from poly(l-lactide) microspheres dispersed in thermosensitive biodegradable gel for combination therapy

Abstract

The objective of the current work was to design an injectable, sustained release formulation of a combination of anticancer drugs, carboplatin and paclitaxel, for localized delivery. In this combination formulation, carboplatin was encapsulated into poly(L-lactide) (PLA) microspheres and paclitaxel was dissolved in thermosensitive biodegradable gel of PLGA-PEG-PLGA (poly (DL-lactide-co-glycolide- polyethylene glycol- poly (DL-lactide-co-glycolide)); no external solvent like cremophorEL was used in the formulation, further, these carboplatin microspheres were dispersed in the gel containing paclitaxel to achieve a single delivery system. The combined formulation was assessed for various parameters for sustained release of both the drugs. Release profiles of carboplatin from PLA microspheres; paclitaxel from hydrogel alone and in combination with carboplatin and carboplatin microspheres dispersed in paclitaxel loaded gel were studied. In vitro release of both the drugs from PLGA-PEG-PLGA hydrogel showed that carboplatin was released with 40-50% burst release and paclitaxel was released in biphasic manner for 50-60 days. Initial burst of carboplatin was controlled by incorporating it in PLA microspheres which were then dispersed in paclitaxel loaded hydrogel and the new formulation did not exhibit any burst release of the drug. Release pattern of combination formulations revealed that the two drugs were co-eluting from a single delivery system and the rate of release of each of the individual drugs was significantly affected. Thus, a novel injectable combination formulation for sustained and simultaneous delivery of carboplatin and paclitaxel was developed which provided sustained release of each of the drugs and could be further explored in tumor models.