Nanoparticle drug delivery system for intravenous delivery of topoisomerase inhibitors

Camptothecin-based drugs, because of their poor solubility and labile lactone ring, pose challenges for drug delivery. The purpose of this research was to develop a nanoparticle delivery system for camptotheca alkaloids. After initial investigations SN-38 was selected as the candidate camptotheca alkaloid for further development. Nanoparticles comprising SN-38, phospholipids and polyethylene glycol were developed and studied in vitro and in vivo. The SN-38 formulations were stable in human serum albumin and high lactone concentrations were observed even after 3 h. In vivo studies in nude mice showed prolonged half-life of the active (lactone form) drug in whole blood and increased efficacy compared to Camptosar(R) in a mouse xenograft tumor model. (C) 2003 Elsevier B.V. All rights reserved.