Box-Behnken Design-响应面优化法优化PEG化和厚朴酚长循环纳米脂质体处方

Formulation optimization of PEGylated long-circulating nanoliposomes entrapped with honokiol by BBD-RSM

采用薄膜-超声分散法制备和厚朴酚长循环纳米脂质体,以包封率为评价指标,考察药脂比(质量比)、磷脂与胆固醇质量比例和m PEG2000-DSPE浓度3个因素对指标的影响,并对各个因素进行二次回归拟合,通过Box-Behnken Design-响应面优化法(BBD-RSM)优选最佳处方.最终优选的处方为和厚朴酚与脂类质量比为1∶20,大豆磷脂与胆固醇质量比为6.71∶1,DSPE-PEG2000浓度为13.38%,药物的平均包封率为92.32%.优化后的处方所制备的脂质体的Zeta电位稳定、粒径分布均匀,Box-Behnken Design-响应面优化法应用简便、预测性好,制备的和厚朴酚长循环纳米脂质体符合设计要求.

Long-circulating nanoliposomes entrapped with honokiol were prepared by the film-ultrasonic dispersion method. Taking the entrapment efficiency（ EE） as indexes,the influence of drug-lipid ratio（ mass ratio）,phospholipid and cholesterol mass ratio and m PEG2000-DSPE concentration was investigated,test results were fitted by binomial nonlinear equations,the formulation optimization of liposome was optimized using Box-Behnken Design-response surface method（ BBD-RSM）. The optimal formulation was honokiol-lipid（1∶ 20）,granulesten-cholesterol（6. 71∶ 1）,the concentration of m PEG2000-DSPE was 13. 38%,the average EE were 92. 32%. The liposomes prepared by the optimized precription had stable Zeta potention and evenly distributed particle size. The response surface method is simple,and of good predictability. The prepared honokiol liposomes satisfy the design requirements.