目的 应用Box-Behnken实验设计，优化水飞蓟素固体脂质纳米粒的最佳处方。方法 采用三因素三水平Box- Behnken实验设计，以水飞蓟素为模型药物，采用乳化蒸发-低温固化法制备固体脂质纳米粒。利用效应曲面法对影响固体脂质纳米粒包封率、载药量和粒径的主要因素进行考察，以包封率、载药量和粒径为响应值，建立相应的二项式数学模型优化处方。结果 最优处方为固体脂质纳米粒中脂质单硬脂酸甘油酯量为5.05%，7.25% Poloxmer 188作为乳化剂，药物的量为15%。结论 采用Box-Behnken实验设计可用于水飞蓟素固体脂质纳米粒的处方优化筛选。

Objective To optimize the formulation parameters of solid lipid nanoparticles (SLN) of silymarin by Box-Behnken experimental design. Methods A three-factor and three-level Box-Behnken experimental design was employed using emulsion evaporation-low temperature solidification technique to prepare SLN with silymarin as model drug. Response surface methodology was used to investigate the factors affecting entrapment efficiency (EE), drug loading (DL), and particle size. Binomial mathematical model-optimized formulation was established with EE, DL, and particle size as response values. Results The optimal formulation was as follows: the amount of glycerol monostearate was 5.05%, the concentration of Poloxamer 188 was 7.25%, and the amount of drug was 15%. Conclusion The Box-Behnken experimental design could be used to optimize the SLN of silymarin.

国家自然科学基金资助项目（81001643，81102820）；广东省科技计划（2011B037100058）