Preparation and cytotoxic activity of hydroxycamptothecin nanosuspensions.

Hydroxycamptothecin is a promising anticancer agent that possesses the ability to inhibit the growth of a wide range of human tumors. Owing to its poor solubility and instability, the pharmaceutical development and clinical utilization of hydroxycamptothecin have been limited. In the present study, a novel precipitation-combined high-pressure homogenization (PCH) technique was used to prepare hydroxycamptothecin nanosuspensions. Based on the homogenization pressure and number of cycles, the process with 10 cycles at 18,000 psi of homogenization pressure was found to be the most efficient method to achieve consistent particle size reduction. It was used to prepare nanosuspensions for characterization and evaluation of the formulation performance. Lyophilization of hydroxycamptothecin nanosuspensions, the shape and crystal form of the drug, and antiproliferative activity were also studied. The mean particle size (z-ave) of the reconstituted freeze-dried powder was small and uniform. The freeze-dried powder might be a good choice for intravenously administrating poorly soluble hydroxycamptothecin, which proved to have higher cytotoxicity against the cancer cells than hydroxycamptothecin injections (p<0.001). Overall, these studies have demonstrated that the PCH technique can be used successfully to prepare hydroxycamptothecin nanosuspensions. Copyright 2010 Elsevier B.V. All rights reserved.