摘要
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.
作者
黄昭峰
徐丽
HUANG Zhaofeng;XU Li(Department of Pharmacy,the People's Hospital of Lishui District of Nanjing,Nanjing 211200,China;Yongyang Street Community Health Service Center of Lishui District of Nanjing,Nanjing 211200,China)
出处
《西北药学杂志》
CAS
2022年第2期94-98,共5页
Northwest Pharmaceutical Journal