载多烯紫杉醇Solutol HS15/Pluronic F127混合胶束的制备及体外评价

Preparation and In Vitro Evaluation of Docetaxel-loaded Solutol HS 15/Pluronic F127 Mixed Micelles

目的:制备载多烯紫杉醇(DTX)的Solutol HS15/Pluronic F127混合胶束系统(SF-DTX),并对处方进行优化,对最佳处方的形态、粒径、包封率、体外释放特性及细胞毒性进行考察。方法:采用薄膜水化法制备该混合胶束体系,通过Doehlert矩阵设计-渴求函数结合法进行处方优化,分别利用透射电镜和激光粒度测定仪对混合胶束的形态、粒径进行表征;采用透析法考察其体外释放行为;采用人非小细胞肺癌A549细胞对混合胶束的细胞毒性进行研究。结果:最优处方制备的SF-DTX的粒径为(22.74±0.43)nm,外观呈球形或类球形,包封率大于90%,制剂24 h体外累积释药百分率为(62.3±2.54)%,且多倍稀释后的稳定性高于单一的胶束体系。SF-DTX对A549细胞的细胞毒性明显高于DTX原料药和空白混合胶束。结论:Solutol HS15/Pluronic F127混合胶束系统的粒径小,稳定性高,可显著增加所载药物的溶解性,且具有一定缓释作用,是一种极具应用前景的抗肿瘤药物给药系统。

Objective： To prepare docetaxel（DTX）-loaded Solutol HS15/Pluronic F127 mixed micelles （SF-DTX）, optimize its formulation and evaluate the properties including shape, particle size, envelop rate, in vitro release characteristic and cytotoxicity of the SF-DTX prepared under the optimized conditions. Methods： The SF-DTX mixed micelles was prepared by thin-film hydration method. Its formu- lation was optimized via the combination of Doehlert Matrix Design method and Desirability Function method. The morphology of SF-DTX was observed under transmission electron microscope（TEM）, and the particle size was measured by laser granulometry. The in vitro release behavior of SF-DTX was determined by the dialysis method. In addition, the in vitro cytotoxicity of SF-DTX was assessed by using human lung adenocarcinoma cell line A549. Results： The SF-DTX prepared based on the optimized formulation showed spherical shape, with a particle size of （22. 74 _＋ O. 43） nm and envelop rate of more than 90%. The 24 h-accumulated release ratio in vitro of the preparation was （62. 3 _＋ 2.54） %. The stability of SF- DTX after multi-fold dilution was higher than that of single micellar system. The cytotoxicity of SF-DTX on A549 cells was significantly stronger than that of free DTX and blank mixed micelles. Conclusion： Solutol HS15/Pluronic F127 mixed micelles exhibits several characteristics, including small particle size, high stability, the capability of improving the solubility of the loaded-drug and sustained release effect. It is a promising delivery system for antieancer drugs.