State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
J Pharm Sci. 2011 Jan;100(1):232-41. doi: 10.1002/jps.22256. Epub 2010 Jun 8.
In attempt to overcome the problem of low water solubility and severe toxicity of camptothecin (CPT) after intravenous administration, a novel drug carrier system based on chitosan (CS) and dibasic sodium phosphate (DSP) has been developed in this paper to encapsulate CPT intending for local administration. Nanocolloids of CPT with size about 500 nm were first prepared, followed by encapsulation in the chitosan/dibasic sodium phosphate (CS/DSP) formulation. The formulation was sol state below 37°C and transformed to nonflowing gel state at 37°C. Encapsulation of CPT nanocolloids had greatly effect on the gelling time as well as the micro-structure of hydrogel. In vitro and in vivo degradation studies revealed that the developed CS/DSP hydrogel was biodegradable and biocompatible. In vitro release study revealed that CPT released from CS/DSP hydrogel in an extended period with about 70% of total CPT released from hydrogel after 18 days. Furthermore, nearly 90% of CPT in the chitosan hydrogels could be preserved in the lactone form (active form) even after 7 days's storage at 37°C. Furthermore, in vitro cytotoxicity of CPT nanocolloids on SKOV3 human ovarian cancer cells suggested the well anti-tumor cell efficiency could be gained at a lower concentration.
为克服喜树碱（CPT）静脉给药后水溶性低和毒性大的问题，本文构建了一种基于壳聚糖（CS）和磷酸氢二钠（DSP）的新型药物载体系统，旨在将 CPT 包裹后用于局部给药。首先制备了粒径约为 500nm 的 CPT 纳米胶粒，然后将其包封于 CS/DSP 制剂中。该制剂在 37°C 以下呈溶胶状态，在 37°C 时转变为非流动凝胶状态。CPT 纳米胶粒的包封对凝胶时间以及水凝胶的微观结构有很大影响。体外和体内降解研究表明，所开发的 CS/DSP 水凝胶是可生物降解和生物相容的。体外释放研究表明，CPT 从 CS/DSP 水凝胶中以延长的时间释放，18 天后约有 70%的总 CPT 从水凝胶中释放。此外，即使在 37°C 下储存 7 天，CS 水凝胶中仍有近 90%的 CPT 能以内酯形式（有效形式）保存。此外，CPT 纳米胶粒对 SKOV3 人卵巢癌细胞的体外细胞毒性表明，较低浓度即可获得良好的抗肿瘤细胞效率。
