Abstract

Purpose: This study intended to prepare a stable hydroxycamptothecin (HCPT) emulsion to characterize the formulation properties and to evaluate the tissue distribution pattern in comparison with the commercially available HCPT injections. Methods: The content of HCPT in the emulsion was measured by HPLC. We also examined the HCPT emulsion in terms of its release behavior and stability in plasma and compared these with the commercially available HCPT injection. After two groups of rats were respectively given HCPT Injection and emulsions intravenously, the drug concentrations in different tissues were determined by HPLC. Results: The chromatographic conditions were highly suitable for analysis of the content of HCPT. HCPT was incorporated into the emulsion at a concentration of 0.1 mg/ml. The mean droplet size and Zeta potential of the emulsion were (178.0±17.0) nm and –(25.1±0.1) mV, respectively. In comparison with the commercially available injection, the dose in the emulsion is just one tenth, but the quantity of lactone from the HCPT in the emulsion was almost equal in both PBS and plasma. The release curve showed that the HCPT emulsion exhibited prolonged-release behaviour. The levels of HCPT in spleen, lung and kidney in emulsion group were slightly higher than that of the injection group. In particular, the concentration of drug in liver increased markedly compared with that in the injection group. Conclusions: The content of the lactone HCPT in the emulsion was higher than in the commercial HCPT injection both in vitro and in vivo. Consequently, the emulsion will have potential HCPT activity against cancer.


Keywords:  10-HCPT   Emulsion   Lactone form   Carboxylate form   Release   Tissue distributions