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

关键词:  羟基喜树碱/mPEG-S-S-C18纳米粒  乳化-溶剂挥发法  星点设计-效应面法  制备工艺

Key words:  hydroxycamptothecin/mPEG-S-S-C18 nanoparticles  emulsifying-solvent evaporation method  central composite design-response surface methodology  preparation process

摘要:

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-Expert V8.0.6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。

Abstract:

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.