黄芪甲苷纳米胶束的制备及Caco-2单层细胞转运研究

Preparation of astrageloside Ⅳ nanomicelles and transport study in Caco-2 cell model

目的制备黄芪甲苷(AST)纳米胶束(AST-NMs),并通过Caco-2单层细胞转运实验评价其渗透性。方法以聚氧乙烯聚氧丙烯醚嵌段共聚物(Pluronic F127)和D-α-维生素E聚乙二醇琥珀酸酯(TPGS)作为载体材料,采用冷冻干燥-水化法制备AST-NMs,并以Pluronic F127与TPGS质量比(X_(1))和聚合物与药物质量比(X_(2))作为变量因素,以AST-NMs的包封率(Y_(1))和粒径分布(Y_(2))作为评价指标,使用中心复合实验设计优化并得到AST-NMs的最优处方;采用差示扫描量热法(DSC)和透射电镜对AST-NMs进行表征;研究了AST-NMs在4种释放介质中的稀释稳定性以及体外药物释放特性;通过Caco-2单层细胞转运实验比较了AST原料药与AST-NMs的渗透性。结果经优化得到AST-NMs的最优处方为:Pluronic F127与TPGS质量比为5∶1,聚合物与药物质量比为38∶1;DSC测定显示,AST-NMs中的药物吸热峰消失;在透射电镜下观察到AST-NMs呈球状分布,无聚集;AST-NMs经不同pH介质稀释后稳定性均较好,在4种释放介质中均表现为平稳的缓慢释药特征;AST-NMs在Caco-2单层细胞的渗透性显著高于AST原料药。结论将AST制备成AST-NMs,可显著提高药物渗透性,有望提高生物利用度。

Objective To prepare astrageloside Ⅳ(AST)nanomicelles(AST-NMs),and to evaluate their permeability by Caco-2 monolayer cell transport experiment in vitro.Methods By using Pluronic F127 and TPGS as carrier materials,AST-NMs were prepared by freeze drying and hydration method.The ratio of Pluronic F127 to TPGS(X_(1))and the ratio polymer to drug(X_(2))were used as variable factors,and the encapsulation efficiency(Y_(1))and particle size distribution(Y_(2))of AST-NMs were used as evaluation indicators,and the central composite design was used to optimize the formulation of AST-NMs.Differential scanning calorimetry(DSC)and transmission electron microscopy were used to characterize the properties of AST-NMs.The dilution stability and in vitro drug release characteristics of AST-NMs in 4 release media were studied.The in vitro permeability of AST drug and AST-NMs was compared by Caco-2 monolayer cell transport experiment.Results The optimal formulation of AST-NMs was as follows:the ratio of Pluronic F127 to TPGS was 5∶1,and the ratio of polymer to drug was 38∶1.The DSC measurement showed that the endothermic peak of AST-NMs disappeared.The AST-NMs were observed to be spherically distributed under transmission electron microscope without agglomeration.The stability of AST-NMs after being diluted with different pH media was relatively good,and they all showed steady slow release characteristics.The AST-NMs had a good stability after being diluted in different pH media.And the AST-NMs exhibited biphasic release characteristics in different pH media.The permeability of AST-NMs in Caco-2 monolayer cells was significantly higher than that of AST drugs.Conclusion The preparation of AST hydrochloride into nanomicelles could significantly improve the permeability and is expected to improve the bioavailability.