【摘要】 目的:制备更昔洛韦壳聚糖纳米粒眼用温敏型原位凝胶并考察其体外释放行为。方法:以离子交联化法制备更昔洛韦壳聚糖纳米粒,考察纳米粒的粒径、包封率等指标,同时观察纳米粒形态,测定纳米粒混悬液的pH及电位等。通过冷溶法将温敏材料溶于混悬液,制备温敏型原位凝胶,并采用星点设计-效应面法优化凝胶制备处方工艺,以人工模拟泪液为释放介质,考察制剂的体外释放特性。结果:更昔洛韦壳聚糖纳米粒呈球形,外观均匀圆整,分散性较好,平均粒径为(208.1±20)nm,多分散指数为0.171±0.030,平均包封率为(16.7±1.35)%,zeta电位为(27.36±2.0)mV;所得温敏型原位凝胶室温下为半透明具蓝色乳光的液体,体温下转变为半固体凝胶。凝胶中更昔洛韦缓释效果较好,其释放在0~4 h符合一级释药动力学过程,4 h之后符合零级动力学过程。结论:更昔洛韦壳聚糖纳米粒温敏型原位凝胶的胶凝效果良好,缓释作用明显,制备工艺简单可行。更多还原

【Abstract】 Objective: To prepare thermosensitive in situ gel containing ganciclovir chitosan nanoparticle for ophthalmic use and to study its in vitro release behavior. Methods: The ganciclovir chitosan nanoparticles( GCV-CS-NPs) were prepared by using the ionotropic gelation method. The diameter and entrapment efficiency of GCV-CS-NPs were studied. The morphology of GCV-CS-NPs was observed,and the pH and zeta potential were measured. Cold dissolution method was applied to prepare the ganciclovir-loaded chitosan nanoparticle thermosensitive in situ gel( GCV-CS-NPs-TISG),by dissolving the thermosensitive material in the GCV-CS-NPs suspension. The formulation of gel was optimized by using the central composite design-response surface methodology. Simulated tear fluid( STF) was applied as release medium to study the in vitro release characteristics of the GCV-CS-NPs-TISG. Results: The GCV-CS-NPs were spherical-like,uniform and non-conglutinated. The mean diameter was( 208. 1 ± 20) nm and the polydispersity index was 0. 171 ± 0. 030. The mean entrapment efficiency was 16. 7% ± 1. 35% and the zeta potencial was( 27. 36 ± 2. 0) mV. The GCV-CS-NPs-TISG was semi-transparent fluid with blue opalescence at room temperature. It turned into semi-solid at body temperature. The release of ganciclovir from gel was in accordance with the first-order kinetics during 0-4 h and the zero-order kinetics after 4 h,indicating that the gel possessed a good controlled release effect. Conclusion: GCV-CS-NPs-TISG has a good gelling effect and sustained release effect. Its preparation technique is simple and feasible.更多还原