Box-Behnken响应面法优化厚朴酚与小檗碱共载脂质体的处方工艺

Formulation optimization of berberine and magnolol co-loaded liposomes by Box-Behnken response surface method

目的:采用Box-Behnken响应面法优化厚朴酚与小檗碱共载脂质体(Lip-MB)的处方工艺。方法:HPLC法同时测定小檗碱、厚朴酚含量。薄膜分散结合pH梯度法制备Lip-MB。在单因素考察基础上,采用Box-Behnken响应面法,以小檗碱和厚朴酚包封率为指标,优选Lip-MB最佳处方和工艺。同时对Lip-MB形态、粒径、Zeta电位、释放度进行评价。结果:最优处方工艺为HSPC与CHOL质量比3.6∶1、药脂比1∶23、外水相pH 8.4、孵育温度59℃。小檗碱和厚朴酚在Lip-MB中的包封率分别为(91.74±1.91)%和(83.17±1.05)%。平均粒径为(106.6±2.60)nm,Zeta电位为(–9.88±2.33)mV,小檗碱和厚朴酚84 h累积释放度分别为98.41%和81.83%。结论:Box-Behnken响应面法所建立的模型可用于Lip-MB的处方工艺优化。优化的Lip-MB包封率较高,粒径小,分布均匀,具有缓释作用。

OBJECTIVE To optimize the formulation of berberine and magnolol co-loaded liposomes(Lip-MB)by Box-Behnken response surface method.METHODS The content of berberine and magnolol was determined by high performance liquid chromatography(HPLC).Lip-MB was prepared by thin-film dispersion plus pH gradient method.Based upon the results of single factor experiment,Box-Behnken response surface method was employed for optimizing the formulation with berberine and magnolol encapsulation efficiency as dependent variables.Morphology,particle size,zeta potential and in vitro release of Lip-MB were evaluated.RESULTS The optimal formulation process was as follow:mass ratio of hydrogenated soybean phosphotidylcholine(HSPC)to cholesterol(CHOL)3.6∶1,drug-to-lipid ratio 1∶23,pH value of external aqueous phase 8.4 and incubation temperature of 59℃.The encapsulation efficiencies of berberine and magnolol in Lip-MB were(91.74±1.91)%and(83.17±1.05)%.Average particle size of liposomes was(106.6±2.60)nm and Zeta potential(–9.88±2.33)mV.Cumulative release rates of berberine and magnolol were 98.41%and 81.83%within 84h respectively.CONCLUSION The model established by Box-Behnken design-response surface method may be employed for optimizing the formulation of Lip-MB.And optimized liposomes offer high encapsulation efficiency,small particle size,uniform distribution and slow release effect.