目的 采用星点设计-效应面法优化异穿心莲内酯固体脂质纳米粒（IA-SLN）处方工艺，并考察其体外释放特性。方法 采用薄膜-超声分散法制备IA-SLN，以包封率、粒径、Zeta电位为评价指标，考察载体比例、投药量、聚山梨酯80质量分数3因素对制备工艺的影响，并对结果进行方程拟合，用效应面法预测最佳工艺条件；采用透析法研究IA-SLN体外释放机制。结果 包封率、平均粒径、Zeta电位都以二项式拟合最优，复相关系数R²分别为0.985 6、0.913 6、0.933 4，根据优化方案制备的IA-SLN包封率96.62%、平均粒径162.4 nm、Zeta电位?31.6 mV。IA-SLN体外释放符合non-Fick’s扩散机制，药物扩散和脂质骨架溶蚀具有协同作用。结论 星点设计-效应面法可用于IA-SLN的工艺优化，所建立的数学模型预测性良好。

Objective To optimize the formulation of isoandrographolide solid lipid nanoparticles (IA-SLN) by central composite design-response surface. Methods IA-SLN were prepared by film-ultrasound dispersing method with entrapment efficiency (EE), diameter, and Zeta potential as evaluation parameters. Effects of carrier ratio, dosage, the concentration of polysorbate 80 on preparation technology were investigated. The results were equations fitted and the optimal conditions were predicted by response surface method. The in vitro release mechanism of IA-SLN was investigated by dialysis method. Results The results showed that EE, mean diameter, and Zeta potential were the best fitted by the second-order polynomial equation, and the multiple correlation coefficients were 0.985 6, 0.913 6, and 0.933 4. Under the optimal condition, the EE, mean diameter, and Zeta potential were 96.62%, 162.4 nm, and ?31.6 mV. IA-SLN in vitro release fitted with non-Fick’s diffusion mechanisms, therefore the drug diffusion and lipid skeleton dissolution had a synergistic effect. Conclusion The central composite design-response surface method is useful for the optimization of IA-SLN preparation. The established model has good prediction.

河南省科技创新人才项目（094100510020）