Abstract
In order to study the in vivo performance and in vitro cytotoxicity of 10-hydroxycamptothecin (10-HCPT) nanosuspension developed in our previous work. For investigating the pharmacokinetics in rats and the tissue distribution in mice with10-HCPT nanosuspension and the 10-HCPT solution, 10-HCPT nanosuspension and 10-HCPT solution were intravenously administered to rats via caudal vein, respectively. And 10-HCPT nanosuspension was intravenously injected to mice to study tissue distribution as compared to 10- HCPT solution. Serum samples and tissue homogenates were analyzed by HPLC-FD, then pharmaceutics parameters were calculation. In vitro cytotoxicity was also carried out with MCF-7/Ard and PC-3 as cell models. The results showed 10-HCPT nanosuspension could decrease plasma peak concentration and extend plasma circulating time compared to 10-HCPT solution. And the biodistribution test indicated that 10-HCPT nanosuspension can markedly change in vivo distribution pattern in comparison to 10-HCPT solution, and had considerable passive targeting capability to the mononuclear phagocyte systems. The in vitro cytotoxicity test demonstrated 10-HCPT nanosuspension had greater cytotoxicity to cancer cells than the solution, especially for adriamycin-sensitive cells. So the nanosuspensions will be a promising formulation strategy to resolve questions on solubility and increase anti-tumor activity of the poorly soluble anticancer compounds.
Keywords: 10-Hydroxycamptothecin, nanosuspensions, pharmacokinetics, tissue distribution, cytotoxicity.
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