摘要
目的制备载他克莫司的口服复合物胶束,观察其理化性质及体外释药特征。方法采用薄膜超声法以普朗尼克F127-壳聚糖聚合物(F127-CS)和脱氧胆酸钠(DCA)为材料制备他克莫司口服大分子复合物胶束,采用单因素考察和均匀设计筛选最优制备工艺;透视电镜下观察胶束外观形态,激光散射粒度仪测定粒径、Zeta电位,HPLC法测定载药量,荧光探针法测定临界胶束浓度,用动态膜透析法测定其在人工胃液和肠液中的体外释放情况。结果电镜照片显示,他克莫司口服胶束圆整均匀、不粘连,粒径为(55.77±2.23)nm,Zeta电位为(-6.38±0.47)m V,载药量为8.93%±0.20%,临界胶束浓度为2.65×10-3mol/L。体外释放结果显示,他克莫司F127-CS/DCA胶束在人工肠液中的释放速率高于人工胃液。结论 F127-CS/DCA口服胶束具有较高的载药量和p H依赖释放特性,适合作为他克莫司口服给药系统。
Objective To prepare the Tacrolimus-loaded polyion complex micelles and observe their release charac-teristics in vitro.Methods Tacrolimus-loaded polyion complex micelles were prepared by film-ultrasonic method with Plu-ronic F127-chitosan （F127-CS）polymer and sodium deoxycholate （DCA）.Preparation technique and optimal formulation were selected via single factor investigation and uniform design.Morphology of polyion micelles was observed by transmis-sion electron microscope.Diameter distribution and zeta potential of polyion micelles were measured by using laser size scattering determinator.Drug loading capacity （DL%）was determined with the high performance liquid chromatography （HPLC）.Pyrene as a fluorescence probe was used to detect critical micelle concentration （CMC）.In vitro release was e-valuated with dynamic membrane dialysis.Results The electron microscope showed spherical micelles were round and u-niform.The average diameter was （55.77 ±2.23）nm,zeta potential was （-6.38 ±0.47）mV,drug loading capacity （DL%）was 8.93% ±0.20%,and the Critical Micelle Concentration （CMC）was 2.65 ×10 -3 mol/L.In vitro release study suggested that Tacrolimus-loaded F127-CS /DCA micelles showed a pH-dependent release,the release rate in artifi-cial intestinal juice was higher than that in artificial gastric juice.Conclusion F127-CS /DCA polyion micelles have high drug-loading capacity and pH-dependent release characteristics,and are suitable for oral administration of Tacrolimus.
出处
《山东医药》
CAS
北大核心
2016年第42期28-31,共4页
Shandong Medical Journal
基金
国家自然科学基金青年基金项目(81503261)
山东省自然科学基金青年基金项目(ZR2013HQ011)
山东省济南市科技明星计划项目(201406016)
