摘要 目的使用聚乙烯己内酰胺-聚醋酸乙烯酯-聚乙二醇接枝共聚物(Soluplus?)和D-α-维生素E聚乙二醇琥珀酸酯(TPGS)作为载体材料制备蝙蝠葛碱复合纳米胶束(dauricine composite nanomicelles,Dau-CNMs),并通过大鼠ig给药评价其药动学情况。方法采用溶剂蒸发-薄膜分散法制备Dau-CNMs,通过单因素实验筛选了Dau-CNMs处方中Soluplus■与TPGS用量配比;分别考察了Dau-CNMs和蝙蝠葛碱单纯纳米胶束(dauricine single nanomicelles,Dau-SNMs)的微观形态、粒径分布、Zeta电位等理化性质;并通过MTT法评估了Dau-CNMs的细胞毒性,采用Caco-2细胞单层模型评价了蝙蝠葛碱原料药、Dau-SNMs和Dau-CNMs的细胞跨膜转运性质;通过大鼠ig给药比较蝙蝠葛碱混悬液、Dau-SNMs和Dau-CNMs的体内药动学特征。结果经实验筛选得到Dau-CNMs的最优处方:Soluplus■与TPGS用量比为7∶1;在透射电子显微镜下可观察到Dau-SNMs和Dau-CNMs均呈圆整球状分布;Dau-CNMs的细胞毒性较低,且能够有效提高药物的跨膜转运能力;与蝙蝠葛碱混悬液组和Dau-SNMs组比较,Dau-CNMs组大鼠ig给药显著提高了药物达峰浓度和口服生物利用度。结论以Soluplus?与TPGS作为载体材料,将蝙蝠葛碱制备成复合纳米胶束,能够显著增加药物生物利用度。 Objective To prepare dauricine composite nanomicelles(Dau-CNMs)using polyethylene caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer(Soluplus■)and D-α-tocopherol polyethylene glycol succinate(TPGS)as carrier materials and evaluate its pharmacokinetics in rats.Methods The Dau-CNMs were prepared by solvent evaporation-film dispersion method.The amount ratio of Soluplus■and TPGS in the Dau-CNMs formulation was screened by single factor experiment.The microscopic morphology,particle size distribution,Zeta potential of Dau-CNMs and dauricine single nanomicelles(Dau-SNMs)were investigated,respectively.The cytotoxicity of Dau-CNMs was evaluated by MTT method.The Caco-2 cell monolayer model was used to evaluate the transmembrane transport properties of dauricine,Dau-SNMs and Dau-CNMs.The in vivo pharmacokinetic characteristics of dauricine suspension,Dau-SNMs and Dau-CNMs after intragastric administration in rats were compared.Results The optimal formulation of Dau-CNMs as followed:The dosage ratio of Soluplus?and TPGS was 7:1.It could be observed under the transmission electron microscope that Dau-CNMs and Dau-SNMs are distributed in a round spherical shape.Dau-CNMs had low cytotoxicity and could effectively improve the dauricine transmembrane transport ability.Compared with dauricine suspension and Dau-SNMs,Dau-CNMs significantly improved the peak concentration and bioavailability of dauricine.Conclusion This study uses Soluplus?and TPGS as carrier materials to prepare dauricine composite nanomicelles,which could significantly increase the bioavailability of dauricine.
出处 《中草药》 CAS CSCD 北大核心 2021年第8期2276-2284,共9页 Chinese Traditional and Herbal Drugs
基金 河北省自然科学基金项目(H2020207002) 河北省高等学校科学技术研究项目(ZD2018013) 河北经贸大学科研基金重点项目(2017KYZ05)。
关键词 蝙蝠葛碱 复合纳米胶束 溶剂蒸发-薄膜分散法 药动学 生物利用度 dauricine composite nanomicelles solvent evaporation-film dispersion method pharmacokinetics bioavailability
