穿心莲内酯甲氧基聚乙二醇-聚乳酸-羟基乙酸纳米粒处方优化及体外释药考察

目的：优化穿心莲内酯甲氧基聚乙二醇-聚乳酸-羟基乙酸methoxy poly（ethylene glycol）-poly（lactic-co-glycolic acid），mPEG-PLGA]纳米粒处方，并进行体外释药评价。方法：乳化法制备穿心莲内酯mPEG-PLGA纳米粒，Box-Behnken设计-效应面法筛选穿心莲内酯mPEG-PLGA纳米粒最优处方，测定包封率、载药量、粒径及Zeta电位。采用质量分数为5%的甘露醇和乳糖等量混合物作为冻干保护剂，进一步制备成冻干粉，考察体外释药行为。结果：穿心莲内酯mPEG-PLGA纳米粒最佳处方为：mPEG-PLGA用量为589 mg、水相体积为70 mL、聚乙二醇硬脂酸酯15（Solutol HS 15）质量分数为1.2%，包封率为（82.07±1.62）%，载药量为（3.87±0.21）%，粒径为（179.56±9.19）nm，Zeta电位为（-10.91±1.84）mV。穿心莲内酯mPEG-PLGA纳米粒体外释药具有缓释特征，释药过程符合Weibull模型：lnln1/（1-M_t/M_∞）]=0.410 3lnt-1.434 1。结论：可用Box-Behnken设计-效应面法优化穿心莲内酯mPEG-PLGA纳米粒，为后续研究奠定基础。

Formulation optimization of andrographolide mPEG-PLGA nanoparticles and in vitro release study

OBJECTIVE To optimize the formulation of andrographolide mPEG-PLGA nanoparticles, and carry out in vitro drug release evaluation.METHODS Emulsification method was employed to prepare andrographolide mPEG-PLGA nanoparticles. Box-Behnken response surface design method was used to investigate the optimal formulation of andrographolide mPEG-PLGA nanoparticles. Entrapment efficiency, drug loading, particle size and Zeta potential were determined. A mixture of mannitol and lactose with a mass fraction of 5% was used as freeze-drying protectant, lyophilized powder was prepared and the release behavior in vitro was investigated.RESULTS The optimal formulation of andrographolide mPEG-PLGA nanoparticles was as follows:mPEG-PLGA dosage was 589 mg, water phase volume was 70 mL and Solutol HS 15 quality score was 1.2%. The envelopment efficiency, drug loading, particle size and Zeta potential were (82.07±1.62)%, (3.87±0.21)%, (179.56±9.19) nm and (-10.91±1.84) mV, respectively. The drug release in vitro showed obvious sustained-release characteristics, and the release process conformed to the following Weibull model:lnln1/(1-M_t/M_∞)]=0.410 3lnt-1.434 1.CONCLUSION Box-Behnken design-response surface method can be employed to optimize formulation of andrographolide mPEG-PLGA nanoparticles, which lays foundation for the further studies.