阿立哌唑混合纳米胶束的制备与评价  

Preparation and evaluation of aripiprazole mixed nanomicelles

作　　者：巨鲜婷[1] 果秋婷[1] JU Xianting;GUO Qiuting(Xianyang Vocational College,Xianyang 712000,China)

机构地区：[1]咸阳职业技术学院,咸阳712000

出　　处：《西北药学杂志》2021年第4期621-626,共6页Northwest Pharmaceutical Journal

摘　　要：目的以聚氧乙烯聚氧丙烯醚嵌段共聚物(Pluronic F123)和D-α-维生素E聚乙二醇琥珀酸酯(TPGS)作为载体材料,制备阿立哌唑(ARP)混合纳米胶束(ARP-mNMs),并通过Caco-2细胞单层模型评价其体外渗透性,通过大鼠灌胃给药评价其体内吸收情况。方法采用冷冻干燥-水化法制备ARP-mNMs,通过测定混合纳米胶束的临界胶束质量浓度、粒径分布以及药物包封率,最终确定ARP-mNMs处方中TPGS与Pluronic F123的配比,在透射电镜下观察ARP-mNMs的微观形态,并比较ARP乙醇溶液和ARP-mNMs的体外药物释放特性;采用Caco-2细胞单层模型评价ARP原料药与ARP-mNMs的细胞跨膜转运情况;并通过大鼠灌胃给药比较ARP混悬液与ARP-mNMs的体内药动学特征。结果经实验筛选得到ARP-mNMs的最佳处方为:Pluronic F123和TPGS用量比为50∶10;在透射电镜下可观察到ARP-mNMs呈球状分布;ARP-mNMs能有效提高药物的渗透性;与ARP混悬液相比,ARP-mNMs的药物达峰质量浓度和口服生物利用度分别提高了4.14、2.36倍。结论以Pluronic F123和TPGS作为载体材料,将ARP制备成ARP-mNMs,能显著提高ARP的口服生物利用度。Objective To prepare aripiprazole(ARP)mixed nanomicelles(ARP-mNMs)by using polyoxyethylene polyoxyepropylene block copolymer(Pluronic F123)and D-α-tocopheryl polyethylene glycol succinate(TPGS)as carrier materials.The in vitro permeability was evaluated by Caco-2 cell monolayer model,and the in vivo bioavailability was evaluated by intragastric administration in rats.Methods The freeze drying-hydration method was used to prepare ARP-mNMs.By measuring the critical micelle concentration,particle size distribution and drug encapsulation efficiency of the mixed nanomicelles,the ratio of TPGS and Pluronic F123 in the ARP-mNMs formulation was finally determined.The microscopic morphology of ARP-mNMs was observed under transmission electron microscope(TEM),and the in vitro drug release characteristics of ARP ethanol solution and ARP-mNMs were compared.The Caco-2 cell monolayer model was used to evaluate the cell transmembrane transport of APP material and ARP-mNMs.And the in vivo pharmacokinetic characteristics of ARP suspensions and ARP-mNMs were compared by oral administration in rats.Results The optimal formulation of ARP-mNMs was as follows:the amount ratio of Pluronic F123 and TPGS 50∶10.ARP-mNMs could be observed in a spherical distribution under the TEM.ARP-mNMs could effectively improve the permeability of drugs.Compared with oral ARP suspension,the peak concentration and oral bioavailability of ARP-mNMs increased by 4.14 times and 2.36 times,respectively.Conclusion In this study,Pluronic F123 and TPGS were used as carrier materials to prepare ARP-mNMs,which could significantly improve the oral bioavailability of ARP.

关 键 词：阿立哌唑 混合纳米胶束 CACO-2细胞单层模型 渗透性 药动学 生物利用度 

分 类 号：R94[医药卫生—药剂学]