星点设计-效应面法优化紫杉醇-PluronicP123共聚物胶束处方工艺  

Preparation optimization of paclitaxel-loaded Pluronic P123 polymeric micelles by central composite design-response surface method

作　　者：薛继杨[1] 韩丽妹[2] 

机构地区：[1]同济大学附属第一妇婴保健院,上海201204 [2]复旦大学药学院,上海201203

出　　处：《中南药学》2015年第11期1137-1140,共4页Central South Pharmacy

摘　　要：目的以星点设计-效应面法优化紫杉醇-Pluronic P123共聚物胶束处方工艺,以期提高难溶性药物紫杉醇在Pluronic P123载体中的包封率和载药量,并对其理化性质进行表征。方法采用薄膜分散法制备紫杉醇-Pluronic P123胶束,以包封率、载药量和胶束溶液药物浓度为考察指标,紫杉醇投药量和水相用量为自变量,采用星点设计-效应面法优化处方,并对模型进行验证,对粒径、体外释放等理化性质进行表征。结果二次多项式非线性回归模型是描述因素与指标关系的最佳模型,根据所优化处方,制得共聚物胶束的包封率约为85.64%,载药量约为1.68%,平均粒径约为(25.2±2.9)nm,zeta电位为(-11.23±2.64)m V。胶束制剂与普通制剂(Taxol注射液)在4 h内的累积释放分别为50.1%和90.5%,前者具有较强的缓释作用。结论通过采用星点设计-效应面优化法确定的处方工艺,可制备具有较高包封率的紫杉醇-Pluronic P123共聚物胶束,所建模型有较好的实用性和预测性。Pluronic P123可有效增溶难溶性药物紫杉醇,并形成具有较强缓释作用的纳米级共聚物胶束制剂,具有应用于肿瘤治疗的潜力。Objective To prepare a paclitaxel-loaded polymeric micelle based on Pluronic P123 and optimize the formulation with central composite design-response surface method to increase the drug loading coefficient, and explore its properties. Methods Polymeric micelles were prepared with Pluronic P123 by thin-film hydration method. Entrapment efficiency, drug loading coefficient and PTX concentration were used as responses, the amount of paclitaxel and water as variables, the central composite design-response surface method was used to optimize the formulation. The physico-chemical properties were characterized, including micelle size, in vitro release behaviors, etc. ResultsThe relationship between dependent and independent variables was fit to the second-order polynomial equation. The micelle size was（25.225.2±2.9） nm with zeta potential（- 11.23±2.64） mV, entrapment efficiency 85.64%, drug loading coefficient 1.68%, and PTX concentration of 234.63 μg·m L- 1. The cumulative release amount of PTX from P123/PTX micelles and Taxol injection was 50.1% and 90.5% respectively, suggesting a sustained release property.Conclusion PTX-loaded polymeric micelles with high entrapment efficiency, are successfully prepared by central composite design-response surface method. PTX can effectively be solubilized by Pluronic P123 and produce nanoscale polymeric micelles with sustained release characteristics in vitro, and may be used in cancer chemotherapy.

关 键 词：共聚物胶束 星点设计-效应面法 PLURONIC P123 紫杉醇 处方优化 

分 类 号：R944[医药卫生—药剂学]