目的 Box-Behnken设计-效应面法（Box-Behnken design-response surface method，BBD-RSM）优化延胡索乙素（THP）聚乳酸-羟基乙酸共聚物[poly（lactic-co-glycolic acid），PLGA]纳米粒（THP-PLGA-NPs）处方，并进行体外评价。方法 纳米沉淀法制备THP-PLGA-NPs，以包封率、载药量、多分散系数（polydispersity index，PDI）和粒径大小为评价指标，单因素结合BBD-RSM筛选最优处方，采用甘露醇作为冻干保护剂制备成冻干粉，将最优处方进行表征及体外释放实验。结果 最佳处方为PLGA用量为491.8 mg、油水体积比1：5.2、乳化剂质量分数为1.12%。THP-PLGA-NPS包封率为（185.07±1.06）%，载药量为（4.73±0.21）%，粒径为（181.32±7.14）nm，分别与模型预测值接近。体外释药具有明显的缓释特征，释药过程符合Higuchi模型：M_t/M_∞=0.112 4 t^1/2+0.078 0，r=0.987 9。结论 Box-Behnken实验设计可用于THP-PLGA-NPS处方的筛选，且优化后的纳米粒具有缓释作用。

Objective To optimize the formulation of tetrahydropalmatine (THP) poly (lactic-co-glycolic acid) (PLGA) nanoparticles (THP-PLGA-NPs) by Box-Behnken design-response surface method (BBD-RSM), and carry out in vitro evaluation. Methods Nanoprecipitation method was used to prepare THP-PLGA-NPs. Encapsulation efficiency, drug loading, polydispersity index (PDI) and particle size were used as evaluation index, single factor investigation method combined with BBD-RSM to investigate the optimal prescriptions of THP-PLGA-NPs. THP-PLGA-NPs were prepared into lyophilized powder using mannitol as freeze-dried protectors. The optimal formulation was characterized and in vitro release experiments were also carried out. Results The optimal formulation:PLGA dosage was 491.8 mg, oil-water volume ratio was 1:5.2 and surfactant concentration was 1.12%. Envelopment efficiency, drug loading and particle size of THP-PLGA-NPS were (185.07 ±1.06)%, (4.73 ±0.21)% and (181.32 ±7.14) nm, respectively. The results were close to that of predicted values. The drug release in vitro had obvious sustained-release characteristics, and the release process conformed to the Higuchi model:M_t/M_∞=0.112 4 t^1/2 + 0.078 0, r=0.987 9. Conclusion It is feasible to apply BBD-RSM for the formulation optimization of THP-PLGA-NPS, and the optimized PLGA nanoparticles have slow-release effects.

R283.6

国家重大新药创制（2018ZX09210090-002-009）；上海市科委项目（21S21903400）