灯盏花乙素Soluplus/TPGS混合胶束的制备及评价

Preparation and evaluation of scutellarin Soluplus/TPGS mixed micelles

目的采用Box-Behnken响应面法优化灯盏花乙素Soluplus/TPGS混合胶束(Scu-MMs)的制备工艺,考察其体外释放行为,并通过Caco-2单层细胞转运实验评价其渗透性。方法以Soluplus和TPGS作为载体材料,采用薄膜分散法制备Scu-MMs,以包封率为评价指标,采用响应面法优化并得到Scu-MMs的最优工艺条件;采用马尔文粒度仪和透射电镜对Scu-MMs进行表征;用透析袋研究Scu-MMs的体外释放度;用Caco-2单层细胞转运实验比较Scu原料药和Scu-MMs的渗透性。结果Scu-MMs的最优工艺条件:Soluplus与TPGS的比值为8.3∶1、载体与Scu的比值为20.9∶1,水化体积为16.4 mL,Scu的平均包封率为91.45%。Scu-MMs的平均粒径为(19.45±0.05)nm,平均电位为(−7.95±0.72)mV;透射电镜下观察到Scu-MMs呈均匀分散的球形分布;Scu-MMs在3种不同pH介质中释放速率均先快后慢,累积释放度在pH 4.5介质中最高;Scu-MMs在Caco-2单层细胞的渗透性显著高于Scu原料药。结论制备成的Scu-MMs粒径小,可明显提高药物渗透性,为后续药物的开发奠定基础。

Objective The preparation process of scutellarin Soluplus/TPGS mixed micelles(Scu-MMs)was optimized by Box-Behnken response surface method.The release behavior was investigated in vitro,and the permeability was evaluated by Caco-2 single-layer cell transport experiment.Methods Soluplus and TPGS were used as carrier materials to prepare Scu-MMs by using thin film dispersion method.The encapsulation rate was used as evaluation index,and the optimal process conditions of Scu-MMs were optimized by response surface method.The Scu-MMs was characterized by Malvern particle size analyzer and transmission electron microscopy.The release of Scu-MMs in vitro was studied with dialysis bag.The permeability of Scu raw material and Scu-MMS was compared by Caco-2 monolayer cell transport assay.Results The optimal process conditions of Scu-MMs were obtained as follows:the ratio of Soluplus to TPGS was 8.3∶1,the ratio of carrier to Scu was 20.9∶1,the hydration volume was 16.4 mL,and the average entrapment rate of Scu was 91.45%.The average particle size of Scu-MMs was(19.45±0.05)nm and the average potential was(−7.95±0.72)mV.Uniformly dispersed spherical distribution of Scu-MMs was observed under transmission electron microscope.The release of Scu-MMs in 3 different pH media was first fast and then slow down,and the cumulative release rate was highest in the pH 4.5 medium.The permeability of Scu-MMs in Caco-2 monolayer cells was significantly higher than that of Scu raw material.Conclusion The prepared Scu-MMs has a small particle size,which can significantly improve the drug permeability and lay an experimental foundation for the development of subsequent drugs.