治疗耳聋神经生长因子温敏凝胶的制备与体外释放特性研究  

Preparation and in vitro release characteristics of nerve growth factor thermosensitive gel for treating deafness

作　　者：朱紫兰 刘威[2] 王来友[1,2] 庞志清[3] 余雪松[4] 

机构地区：[1] 广东药学院药科学院, 广东省广州510006 [2] 广东药学院中医药研究院, 广东省广州510006 [3] 复旦大学药学院药剂学教研室 [4] 广东药学院生科院, 广东省广州510006

出　　处：《中国基层医药》2014年第8期1121-1123,I0002,共4页Chinese Journal of Primary Medicine and Pharmacy

基　　金：国家自然科学基金项目（81102502）;广东省医学科研基金项目（B2008080）

摘　　要：目的 制备治疗耳聋的多肽类药物神经生长因子（NGF）温度敏感缓释凝胶给药系统并考察其体外释放规律,为内耳疾病治疗中的大分子药物递送系统设计提供参考.方法 以神经生长因子为主药,Pluronic F127为凝胶基质,考查凝胶基质浓度对低临界溶解温度（LCST）的影响,采用无膜溶出法评价其体外释放行为,反高效液相色谱法测定NGF温敏凝胶体外释药量.结果 含不同浓度Pluronic F127的hβ-NGF温敏原位凝胶的平均低临界溶液温度为28.48～36.26℃,制剂较稳定,体外释放符合零级动力学特征,累积释放率均达95％以上,Pluronic F127浓度越高缓释特征越明显.结论 NGF温度敏感凝胶可望成为一种治疗耳聋的的新型内耳给药系统,值得进一步开发研究.Objective To prepare polypeptide nerve growth factor （NGF） thermosentitive gel and observe drug release in vitro,in order to provide scientific information for biopharmaceuticals delivery system design aiming to treat the inner disease.Methods The thermosensitive in situ gel was prepared with NGF as main component and Pluronic F127 as the gel matrixes.The effect of concentration of gel matrix PF127 on lower critical solution temperature（LCST） were investigated.In vitro release kinetic studies were performed using membraneless dissolution method and reversed-phase high performance liquid chromatography （HPLC） method was adopted to determine NGF content in the dissolution medium.Results The average LCST of NGF-loaded gel prepared by different concentration of PF127 was 28.48-36.26℃ and the gels had good stability.The in vitro release kinetics was well characterized by sustained release and can be fitted by zero order kinetics.The in vitro accumulated release ratio of NGF in the thermosensitive gel reached to above 95%.hβ-NGF loaded in higher PF127 gel resulted in a more sustained release of hβ-NGF from the thermosensitive gel.Conclusion Well-prepared NGF thermosensitive gel is a promising inner ear-oriented drug delivery system for treating deafness and deserves to further development.

关 键 词：神经生长因子 耳聋 温敏凝胶 缓释剂 体外释放率 

分 类 号：R944[医药卫生—药剂学]