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中国药学(英文版) ›› 2019, Vol. 28 ›› Issue (8): 561-570.DOI: 10.5246/jcps.2019.08.054

• 【研究论文】 • 上一篇    下一篇

提高难溶药物小肠吸收的靶向寡肽转运体PepT1的聚合物胶束的制备与表征

靳尧, 刘琦, 周楚杭, 韩诗迪, 周远航, 胡新平, 王乐淇, 刘艳*   

  1. 北京大学药学院 分子药剂学与新释药系统北京市重点实验室, 北京 100191
  • 收稿日期:2019-04-15 修回日期:2019-05-18 出版日期:2019-09-02 发布日期:2019-06-07
  • 通讯作者: Tel.: +86-10-82801508, E-mail: yanliu@bjmu.edu.cn
  • 基金资助:

    National Natural Science Foundation of China (Grant No. 81673366) and the National Key Science Research Program of China (973 Program, Grant No. 2015CB932100).

Construction and characterization of intestinal oligopeptide transporter PepT1-targeted polymeric micelles for enhanced intestinal absorption of poorly water-soluble agents

Yao Jin, Qi Liu, Chuhang Zhou, Shidi Han, Yuanhang Zhou, Xinping Hu, Leqi Wang, Yan Liu*   

  1. Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
  • Received:2019-04-15 Revised:2019-05-18 Online:2019-09-02 Published:2019-06-07
  • Contact: Tel.: +86-10-82801508, E-mail: yanliu@bjmu.edu.cn
  • Supported by:

    National Natural Science Foundation of China (Grant No. 81673366) and the National Key Science Research Program of China (973 Program, Grant No. 2015CB932100).

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摘要：

为克服小肠上皮这一药物口服吸收的主要屏障, 进一步提高难溶药物的口服吸收, 本研究设计并合成了偶联小肠上皮广泛分布的寡肽转运体PepT1的底物Gly-Sar的聚乙二醇-聚乳酸嵌段共聚物(Gly-Sar-PEG-b-PLA), 制备并表征了靶向PepT1的聚合物胶束。用薄层色谱和核磁共振氢谱对其结构进行了确证和表征, 用凝胶渗透色谱测定聚合物的分子量为5954 g/mol, 多分散性指数为1.34。由Gly-Sar-PEG-b-PLA制备的载DiI的聚合物胶束的粒径为40.36 nm, 多分散性指数为0.294, 透射电镜观察胶束呈规则的球形, 载药量为0.076%。此外, 所制备的靶向PepT1的聚合物胶束增强了难溶药物的小肠吸收。因此, 其在难溶药物的口服递送方面具有一定的潜力。

关键词: 小肠转运体, 寡肽转运体PepT1, 甘氨酰肌氨酸, 聚合物胶束, 口服给药

Abstract:

To overcome the main barrier of intestinal epithelium for the oral absorption of poorly water-soluble drugs and further improve their oral absorption, Gly-Sar, the substrate of the oligopeptide transporter PepT1 widely distributed in the small intestine,conjugated poly(ethylene glycol)-block-poly(D,L-lactide) (Gly-Sar-PEG-b-PLA) was designed and synthesized, and PepT1-targetedpolymeric micelles were prepared and characterized. The structure of the synthesized Gly-Sar-PEG-b-PLA was confirmed by use of TLC and 1H-NMR. The average molecular weight measured by GPC was 5954 g/mol with PDI of 1.34. The DiI-loaded polymeric micelles from Gly-Sar-PEG-b-PLA with drug loading content of 0.076% were characterized to exhibit 40.36 nm in diameter with PDI of 0.294, and well-defined spherical shape observed by TEM. Furthermore, the PepT1-targeted polymeric micelles profoundly enhanced intestinal absorption of poorly water-soluble drug. Therefore, the designed PepT1-targeted polymeric micelles might have a promising potential for oral delivery of water-insoluble drugs.

Key words: Intestinal transporter, Oligopeptide transporter PepT1, Gly-Sar, Polymeric micelles, Oral administration

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