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2025年6月11日 15:38 星期三
首页 > 过刊浏览>2021年第52卷第8期 >2021,52(8):2276-2284. DOI:10.7501/j.issn.0253-2670.2021.08.010
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蝙蝠葛碱复合纳米胶束的制备及大鼠体内药动学研究

Preparation and pharmacokinetic evaluation of dauricine composite nanomicelles in rats

发布日期：2021-04-22
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    [关键词]
    [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。
    [Key word]
    [Abstract]
    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.
    [中图分类号]
    R283.6
    [基金项目]
    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）
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