【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。更多还原

【Abstract】 Objective To prepare the Tacrolimus-loaded polyion complex micelles and observe their release characteristics in vitro. Methods Tacrolimus-loaded polyion complex micelles were prepared by film-ultrasonic method with Pluronic 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 transmission 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 evaluated with dynamic membrane dialysis. Results The electron microscope showed spherical micelles were round and uniform. The average diameter was( 55. 77 ± 2. 23) nm,zeta potential was(-6. 38 ± 0. 47) m V,drug loading capacity( DL%) was 8. 93% ± 0. 20%,and the Critical Micelle Concentration( CMC) was 2. 65 × 10-3mol / L. In vitro release study suggested that Tacrolimus-loaded F127-CS / DCA micelles showed a p H-dependent release,the release rate in artificial intestinal juice was higher than that in artificial gastric juice. Conclusion F127-CS / DCA polyion micelles have high drug-loading capacity and p H-dependent release characteristics,and are suitable for oral administration of Tacrolimus.更多还原