Mixed PEG-PE/vitamin E tumor-targeted immunomicelles as carriers for poorly soluble anti-cancer drugs:: Improved drug solubilization and enhanced in vitro cytotoxicity

Two poorly soluble, potent anti-cancer drugs, paclitaxel and camptothecin, were successfully solubilized by mixed micelles of polyethylene glycol-phosphatidyl ethanolamine (PEG-PE) and vitamin E. Drug-containing micelles were additionally modified with antinucleosome monoclonal antibody 2C5 (mAb 2C5), which can specifically bring micelles to tumor cells in vitro. The optimized micelles had an average size of about 13-22 nm and the immuno-modification of micelles did not significantly change it. The solubilization of both drugs by the mixed micelles was more efficient than by micelles made of PEG-PE alone. solubilization of camptothecin in micelles prevented also the hydrolysis of active lactone form of the drug to inactive carboxylate form. Drug-loaded mixed micelles and mAb 2C5-immunomicelles demonstrated significantly higher in vitro cytotoxicity than free drug against various cancer cell lines. (c) 2008 Elsevier B.V. All rights reserved.