多柔比星聚酯微球的制备

Optimized Preparation of Doxorubicin-loaded Poly(β-hydroxybutyrate) Microspheres

采用液中干燥法制备多柔比星聚酯微球,使用星点设计-效应面法优化制备工艺。以药物与药物和聚β-羟基丁酸酯(PHB)总量的重量比、有机相中PHB浓度和水相中聚乙烯醇(PVA)浓度为自变量,载药量、包封率、粒径和跨距为因变量,分别进行多元线性回归和二次多项式拟合。结果表明,4个方程均采用二次多项式拟合的效果较好。根据因变量效应面选择的较佳工艺条件为药物与药物和PHB总量之比6%、PHB浓度50mg/ml、PVA浓度6.5%,按优化工艺制得的微球形态圆整,载药量、包封率、平均粒径和跨距分别为1.0%、16.8%、43.1μm和1.45,体外释放60d累积释放65%。

Doxorubicin microspheres were prepared by an in-liquid drying method and optimized using a centralcomposite design. Multiple linear regression equation and quadratic polynomial equation were fitted by the ratio of drug tothe total weight of drug and poly(β-hydroxybutyrate)(PHB), PHB concentration in organic phase and polyvinyl alcohol(PVA) concentration in aqueous phase as independent variables, and drug loading, encapsulation efficiency, mean diameterand span as dependent variables, respectively. The results showed that all the four equations were well fitted to quadraticpolynomial equations. The optimal conditions were: the ratio of drug to drug and PHB 6%, PHB concentration 50mg/ml andPVA concentration 6.5%. The prepared microspheres were smooth and spherical. Drug loading, encapsulation efficiency,mean diameter and span were 1.0%, 16.8%, 43.1μm and 1.45, respectively. In vitro accumulative release reached 65% in 60d.