Preparation and antitumor study of camptothecin nanocrystals

Camptothecin (CPT) is a potent, broad spectrum antitumor agent that inhibits the activity of DNA topoisomerase I. Due to its poor solubility and stability and consequent delivery challenges, its clinical use is nevertheless limited. We aim to use nanocrystal formulation as a way to circumvent the difficult solubilization practice. Specifically, camptothecin nanocrystals were prepared with a sonication-precipitation method without additional stabilizing surfactants. Particle characteristics, cellular cytotoxicity, and animal antitumor effect were examined. CPT nanocrystals were tested to be more potent to MCF-7 cells than CPT solution in vitro. When tested in MCF-7 xenografted BALB/c mice, the CPT nanocrystals exhibited significant suppression of tumor growth. The drug concentration in the tumor was five times more at 24 h by using the nanocrystal treatment than by using the drug salt solution. Storage stability study indicated that the nanocrystals were stable for at least six months. Overall, CPT nanocrystals were considered to be potentially feasible to overcome formulation challenges for drug delivery and to be used in clinic. (C) 2011 Elsevier B.V. All rights reserved.