环孢素眼植入凝胶膜制备及其体外释放探究.docVIP

环孢素眼植入凝胶膜制备及其体外释放探究摘要：目的以交联透明质酸为载体制备环孢素眼植入凝胶膜，观察其体外药物释放特性。方法以酰肼为交联剂，将环孢素与透明质酸钠混合后反应形成载药凝胶膜；采用等距浸出法测定载药凝胶膜的体外释放度，绘制它在2种不同释放介质中的体外释放曲线，探讨透明质酸酶对其药物释放的影响。结果环孢素眼植入凝胶膜载药率为(2.90±0.14) ％(n＝5)；在等渗磷酸盐缓冲溶液中释放缓慢且恒定，28 d内药物释放符合零级动力学方程；在含有透明质酸酶的释放介质中，药物释放速度加快，并随凝胶中透明质酸的降解速度而变化。结论环孢素眼植入凝胶膜是一种有开发价值的眼植入缓释制剂。 关键词：环孢素；交联透明质酸；眼植入剂；缓释 中图分类号：R988.1文献标识码：A文章编号：1672-979X(2008)11-0015-04 Preparation of Cyclosporin Hydrogel Film for Eye Implant and Study on Drug Release in vitro CHEN Jian-ying, LING Pei-xue, HE Yan-li*, LIU Jie, WANG Min (Institute of Biopharmaceuticals of Shandong Province, Jinan 250108, China) Abstract：Objective To prepare cyclosporin hydrogel film for eye implant with cross-linked hyaluronic acid derivatives as vehicle, and evaluate drug release properties in vitro of the hydrogel film. Methods Cyclosporin and sodium hyaluronate were mixed to form hydrogel film with acid hydrazide as a cross-linking agent. The drug release rate of the hydrogel film in vitro was measured by equal distance release method. The release curves of the hydrogel film in two media were drawn, which could be used to evaluate the effect of hyaluronidase（HAse）on the release of cyclosporin. Results The drug loading of the hydrogel film was (2.90±0.14) ％（n＝5）. The release of cyclosporin from the hydrogel film was slow and significantly sustained and the drugrelease pattern followed a zero-order kinetics equation in isotonic phosphate buffered solution during the first 28 d. The release rate of cyclosporin was increased in the medium with HAse and it changed following the degradation rate of hyaluronate. Conclusion Cyclosporin hydrogel film made of cross-linked hyaluronic acid derivatives can be a worthwhile development as a sustained-release preparation for eye implant. Key words：cyclosporin; cross-linked hyaluronic acid; eye implant; sustained release 环孢素（cyclosporin）是一种选择性免疫抑制剂，目前临床常用于抗器官移植排斥反应。眼科使用环孢素滴眼剂主要用于治疗角膜移植排异反应、自身免疫性眼病以及干眼症[1]。文献报道，环孢素用于青光眼小梁手术还具有促进滤泡形成、抑制滤泡成纤维细胞增殖和过滤通