Box-Behnken效应面法优化姜黄素纳米结构脂质载体处方

Formulation optimization of curcumin loaded nanostructured lipid carriers by Box-Behnken experimental design

目的采用Box-Behnken效应面法优化处方,制备姜黄素纳米结构脂质载体,并考察其理化性质。方法采用薄膜超声法制备载药纳米结构脂质载体,分别以药物质量浓度(X1)、总脂质质量浓度(X2)和混合乳化剂质量浓度(X3)为考察对象,以包封率(Y1)、粒径(Y2)为评价指标,利用三因素三水平Box-Behnken效应面设计法筛选载药纳米结构脂质载体的最佳处方。采用微柱离心法测定制剂的包封率,透射电镜观察其外观形态,动态光衍射法测定其粒径及Zeta,差示扫描量热法确证姜黄素在载体中的分散状态。结果最优处方制备的载药纳米结构脂质载体外形呈圆形或椭球形,粒径分布均匀,平均粒径为(58.37±2.60)nm,Zeta电位为-(22.6±0.88)mV,包封率为(93.48±0.86)%,DSC结果表明药物以非结晶状分散于纳米结构脂质载体中。结论采用Box-Behnken效应面法优化姜黄素纳米结构脂质载体处方是可行的。

Objective To optimize the formulation of curcumin loaded nanostructured lipid carriers by Box-Behnken design and investigate its physic-chemical properties.Methods Curcumin loaded nanostructured lipid carriers were prepared by film-dispersion and ultrasonication method.A three factor,three-level Box-Behnken design was employed,with the amount of the drug concentration（X1）,mixed lipid（X2） and emulsifier mixture concentration（X3） as the investigation object.The evaluation indexes were the entrapment efficiency particle size（Y1） and particle size（Y2）.Transmission electron microscopy（TEM） was employed to study the shape.Dynamic light scattering was used to study the particle size and electric potential.The entrapment efficiency was determined by mini-column centrifugation.Results In the optimized formulation,the shape of NLC was round or ellipsoidal with the particle size of（58.37 ± 2.60）nm,the many dispersion index（P.I.） was 0.207,entrapment efficiency was（93.48 ± 0.86）% and Zeta potential was-（22.6 ± 0.88）mV.DSC showed that the drug was dispersed in the nanoparticles of non-crystalline.Conclusions The Box-Behnken design is effective and suitable for optimizing the formulation of curcumin loaded nanostructured lipid carriers.