Box-Behnken设计-效应面法优化根皮素纳米结构脂质载体处方研究

目的： Box-Behnken设计-效应面法优化根皮素纳米结构脂质载体处方。方法： 乳化超声法制备根皮素纳米结构脂质载体,采用包封率（Y₁）和粒径（Y₂）作为考察指标,选择脂-药比（X₁）、固液脂质比（X₂）、表面活性剂浓度（X₃）为主要影响因素,通过二次多元回归模型拟合根皮素纳米结构脂质载体的影响因素与响应值之间的关系,绘制模型效应面图,并验证最佳处方。结果： 最佳处方为：脂-药比为16.4,固液脂质比为4.7,表面活性剂浓度为1.3%。所得3批根皮素纳米结构脂质载体包封率分别为85.7%、84.9%和85.1%;粒径分别为166.9 nm、168.4 nm和170.3 nm,与模型预测值接近。制备的根皮素纳米结构脂质载体基本外貌为圆形,无粘连现象。根皮素存在状态由结晶态转变为无定型态。体外释药具有明显的缓释特征,释药过程符合Weibull模型。结论： Box-Behnken实验设计可用于根皮素纳米结构脂质载体处方的筛选,为后续体内外研究奠定了基础。

Formulation optimization of phloretin nanostructured lipid carrier by Box-Behnken design-response surface method

OBJECTIVE To employ the Box-Behnken design-response surface method for optimizing the formulation of phloretin nanostructured lipid carrier(PNLC). METHODS Emulsion ultrasonic method was utilized for preparing PNLC.Envelopment efficiency(Y₁) and particle size(Y₂) were used as the evaluation standard and the effects of lipid-drug ratio(X₁), solid-liquid lipid ratio(X₂) and surfactant concentration(X₃) selected as major influencing factors.Second-order equation was utilized for estimating the relationship between independent and dependent variables.Response surface was drawn and optimal formulation validated.RESULTS Optimal formulation:lipid-drug ratio was 16.4, solid-liquid lipid ratio 4.7 and surfactant concentration 1.3%.Its envelopment efficiency and particle size were 85.7%, 84.9%, 85.1% and 166.9 nm, 168.4 nm and 170.3 nm respectively.The results approximated the predicted values.The appearances of prepared PNLC were spherical and non-adhesive.The existential state of phloretin altered from crystalline to amorphous.Its in vitro drug release displayed obvious sustained-release characteristics and the release process conformed to the Weibull model.CONCLUSION It is feasible to apply Box-Behnken design-response surface method for optimal formulation of PNLC, laying a theoretic foundation for subsequent in vitro and in vivo studies.