A micellar prodrug of paclitaxel conjugated to cyclotriphosphazene

Abstract

A novel water soluble and biodegradable cyclotriphosphazene-paclitaxel conjugate was prepared by reacting 2′-succinyl paclitaxel with cyclotriphosphazenes bearing equimolar glycyl-l-lysine and methoxy poly(ethylene glycol) as side groups. The macromolecular conjugate was found to self-assemble in aqueous solution to form stable micelles with a mean hydrodynamic diameter of 24.7 nm and a low critical micelle concentration of 10 mg/L. The present conjugate exhibited lower than free paclitaxel but reasonably high in vitro cytotoxicity against selected human tumor cells due to their hydrolytic degradation in PBS solution. © 2008 Elsevier Ltd. All rights reserved.