星点设计——效应面法优化小檗碱Pluronic F127聚合物胶束制备工艺  

Optimization of Preparation of Berberine-loaded Pluronic F127 Polymeric Micelles by Central Composite Design/Response Surface Methodology

作　　者：黄凤杰[1] 沈彦君[1] 胡阳[1] 张峻颖[2] 吴春勇[3] 

机构地区：[1]中国药科大学生命科学与技术学院,江苏南京210009 [2]中国药科大学中药学院,江苏南京210009 [3]中国药科大学药学院,江苏南京210009

出　　处：《药物生物技术》2015年第4期307-311,共5页Pharmaceutical Biotechnology

基　　金：国家自然科学基金(No.81102819);江苏省自然科学基金(No.BK2012358);高等学校博士学科点专项科研基金(No.20120096120004);中央高校基本科研业务费(No.PY2014ZY0005);大学生创新药物研制能力提高项目(No.J1030830)

摘　　要：制备盐酸小檗碱Pluronic F127共聚物胶束,并通过星点设计——效应面法优选其处方。利用薄膜水化法制备盐酸小檗碱Pluronic F127共聚物胶束,在单因素试验的基础上,选取影响显著的因素作为自变量,以包封率和载药量作为考察指标,进行2因素5水平的中心组合响应面优化实验设计(也称星点设计——效应面法),并进行多项式非线性方程拟合,优选最佳处方工艺并进行验证。最优处方工艺为Pluronic F127/小檗碱质量比6.9,水化体积13.14 m L;得到的胶束包封率为96.55%,与预测值97.71%相对误差仅1.19%;载药量为12.09%,与预测值12.36%相对误差仅2.18%,理论载药量为12.64%,实际载药量达到了理论载药量的95.65%。应用星点设计——效应面优化法能够精确有效地优化小檗碱Pluronic F127聚合物胶束的制备工艺。为提高胶束稳定性进行冻干得到胶束冻干制剂再分散性良好,可在4℃保存至少一个月,仍具有较高的包封率。Berberine-loaded Pluronic F127 micelles were prepared to improve the poor solubility of BER and the preparation formulation was optimized by central composite design-response surface methodology. Berberine-loaded Pluronic F127 micelles were prepared by thin-film hydration method. On the basis of single factor experiments,the remarkable affecting factors as independent variables,the entrapment efficiency（ EE%） and the drug-loading（ DL%） as dependent variables,the formulation was designed and optimized by two factors and five levels Central Composite Design,and fitted by polynomial nonlinear equation,to choose and verify the best preparation process. As a result,the optimum formulation was as follows： mass ratio of Pluronic F127 / BER 6. 9,hydration volume 13. 14 m L. Under the optimum conditions,the entrapment efficiency（ EE%） was 96. 55%,and the predicted value was97. 71%,the relative error was only 1. 19% between experimental value and predicted values. Meantime,the drug-loading（ DL%）was 12. 09%,and the predicted value was 12. 36%,and the relative error was only 2. 18% between experimental value and predicted values. And actual drug loading reached 95. 65% of the theoretical drug loading which was 12. 64%. Therefore,central composite design and response surface methodology can precisely and effectively optimize the preparation of berberine-loaded Pluronic F127 polymeric micelles. The lyophilized micelles were in good redispersibility. It can be stored at least one month at 4 ℃,still having a high encapsulation efficiency.

关 键 词：小檗碱 普朗尼克F127 聚合物胶束 单因素考察 星点设计-效应面法 处方优化 

分 类 号：R284.2[医药卫生—中药学] TQ460.6[医药卫生—中医学]