星点设计-效应面法优化羟基喜树碱/mPEG-S-S-C18纳米粒的制备工艺

Optimization of the Preparation of Camptothecin Loaded mPEG-S-S-C18 Nanoparticles by Central Composite Design-response Surface Method

目的制备载羟基喜树碱(hydroxycamptothecin,HCPT)还原响应mPEG-S-S-C18纳米粒,采用星点设计-效应面法筛选优化制备工艺。方法采用乳化-溶剂挥发法制备HCPT/mPEG-S-S-C18纳米粒,应用单因素法考察投药量、水相/油相体积比、超声功率以及超声时间对载药纳米粒包封率和载药量的影响。在此基础上,以包封率和载药量作为评价指标,采用Design-ExpertV8.0.6软件进行星点设计,优化载药纳米粒的制备工艺。结果优化获得的HCPT/mPEG-S-S-C18纳米粒制备工艺投药量为1.0 mg,水相/油相体积比为4.56∶1,超声功率为562.5 W。该工艺制备的载药纳米粒包封率为(58.14±1.04)%,载药量为(3.46±0.22)%,平均粒径为(322.9±9.52)nm,多分散性指数为0.195±0.05,Zeta电位为(-17.5±2.11)mV。结论乳化-溶剂挥发法适用于制备HCPT/mPEG-S-S-C18纳米粒,星点设计-效应面法可优化获得载药纳米粒的最佳制备工艺,所得的载药纳米粒包封率和载药量较高,所建立的数学模型预测性良好。

OBJECTIVE To prepare redox-responsive mPEG-S-S-C18 nanoparticles loaded with hydroxycamptothecin(HCPT)and optimize preparation process of the nanoparticles by central composite design-response surface methodology.METHODS HCPT/mPEG-S-S-C18 nanoparticles were prepared by emulsifying-solvent evaporation method.The influence of the drug dosage,water phase/oil phase volume ratio,ultrasonic power and ultrasonic time on the entrapment efficiency and drug loading capacity of HCPT/mPEG-S-S-C18 nanoparticles were investigated respectively by single factor mwthod.Then,with the entrapment efficiency and drug loading capacity as the indexes,the preparation process of HCPT/mPEG-S-S-C18 nanoparticles was optimized by central composite design-response surface method with Design-Expert V8.0.6 software.RESULTS The optimal preparation process of HCPT/mPEG-S-S-C18 nanoparticles was as followed:the drug dosage of 1.0 mg,water phase/oil phase volume ratio of 4.56∶1,ultrasonic power of 562.5 W.The entrapment efficiency,drug loading capacity of HCPT/mPEG-S-S-C18 nanoparticles prepared by the optimal process were(58.14±1.04)%and(3.46±0.22)%,respectively,with average particle size of(322.9±9.52)nm,polydispersity index of 0.195±0.05 and Zeta potential of(-17.5±2.11)mV.CONCLUSION The emulsifying-solvent evaporation method is feasible to prepare HCPT/mPEG-S-S-C18 nanoparticles.The central composite design-response surface method is suitable for optimization of the preparation of HCPT/mPEG-S-S-C18 nanoparticles with high entrapment efficiency and drug loading capacity.The established mathematical model is predictive.