N-三甲基壳聚糖包覆司帕沙星纳米脂质体原位凝胶的研制及体外释药研究

Preparation and Drug Release in vitro of N-Trimethyl Chitosan-coated Sparfloxacin Nanoliposomes in SituGels

目的:制备眼用N-三甲基壳聚糖(TMC)包覆的司帕沙星(SL)纳米脂质体原位凝胶(ISG),并考察其体外释放度。方法:采用p H梯度法制备SL脂质体,经高压均质至纳米级,用TMC包衣。以胶凝温度为指标,优选ISG基质泊洛沙姆407的最佳浓度,采用冷法制备TMC包覆SL纳米脂质体ISG。对TMC包覆SL纳米脂质体ISG中脂质体的形态、粒径、Zeta电位及包封率进行考察;以TMC包覆SL纳米脂质体为对照,采用无膜溶出模型考察其体外释药特性。结果:泊洛沙姆407的最佳浓度为25%,在人工泪液中的胶凝温度为23.6℃,稀释后的胶凝温度为33.5℃。TMC包覆SL纳米脂质体ISG中脂质体形态圆整,平均粒径为(96.8±1.5)nm,Zeta电位为(46.2±1.4)m V,包封率为(76.6±2.4)%,与TMC包覆SL纳米脂质体相比无明显变化。TMC包覆SL纳米脂质体ISG药物释放和凝胶溶蚀均为符合零级动力学特征,且与TMC包覆SL纳米脂质体相比,缓释性更为显著。结论:TMC包覆SL纳米脂质体ISG胶凝温度理想,并可延缓药物释放。

Objective：To prepare N-trimethyl chitosan （TMC）-coated sparfloxacin （SL） nanoliposomes in situ gels（ISG）and in-vestigate the drug release in vitro.Methods：SL liposomes were prepared by a pH gradient method , and then homogenized to nanolipo-somes by high pressure .TMC was used as the coating material to prepare TMC-coated SL nanoliposomes .Poloxamer 407 was used as the gel base, and the optimal amount was selected according to the gelation temperature .TMC-coated SL nanoliposomes ISG was pre-pared using a cold method , and the morphology , size, zeta potential and entrapment efficiency of TMC-coated SL nanoliposomes were studied.A membraneless model was used to study the drug release in vitro, and the result was compared with that of TMC-coated SL nanoliposomes.Results：The optimal amount of poloxamer 407 in the formula was 25%, and the gelation temperature was 23.6℃in the artificial tears and 33 .5℃in the diluted artificial tears .The morphology of TMC-coated SL nanaoliposomes in the ISG was spherical with the mean diameter of （96.8 ±1.5） nm, zeta potential of （46.2 ±1.4） mV and entrapment efficiency of （76.6 ±2.4） %, and the indices had no significant difference when compared with those of TMC-coated SL nanoliposomes .Both the drug release in vitro and gel dissolution profile of TMC-coated SL nanoliposomes ISG exhibited the characteristics of zero-order kinetics, and compared with that of TMC-coated SL nanoliposomes , the sustained release property of the ISG was more significant .Conclusion：TMC-coated SL nanoli-posomes ISG has promising gelation temperature and notable sustained release property .