BACKGROUND: Camptothecin (CPT) is a well-established topoisomerase I inhibitor against a broad spectrum of cancers. However, poor aqueous solubility, instability, and toxic effects to normal tissues have limited CPT clinical development. Recently, sterically stabilized micelles (SSM) composed of polyethylene glycol (PEGylated) phospholipids have been introduced as safe, biocompatible nanocarriers for the delivery of poorly water-soluble drugs. It was the aim of this study to develop and evaluate in vitro camptothecin-containing SSM (CPT-SSM) as a novel nanomedicine for parenteral administration. METHODS: The solubilization potential, stability, and in vitro cytotoxicity of CPT in SSM were studied. Lyophilization of CPT-SSM under controlled conditions was also studied. RESULTS: The mean size of CPT-SSM was found to be approximately 14 nm with a narrow size distribution. CPT-SSM were prepared by coprecipitation reconstitution. At a concentration of 15 mmol/L of PEGylated phospholipids where no micelle-micelle interaction was observed, CPT solubilization in SSM was 25-fold higher than CPT in buffer. We determined that CPT can be solubilized in SSM up to molar ratios of CPT/lipid = 0.0063:1. Above this critical molar ratio, heterogeneous systems of CPT-SSM and CPT self-aggregated particles were formed. CPT in SSM was at least 3 times more stable and 3-fold more cytotoxic to MCF-7 cells than CPT alone. Furthermore, CPT-SSM alone was lyophilized without additional lyoprotectants and cryoprotectants and reconstituted without any significant change in properties. CONCLUSION: We have shown that CPT in SSM is a promising nanomedicine with improved drug solubility, stability, freeze-drying properties, and anticancer activity. It is anticipated that, because of the nanosize and steric stability of the micelles, CPT-SSM will be passively targeted to solid cancers in vivo, resulting in high drug concentration in tumors and reduced drug toxicity to the normal tissues.