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

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（英文）

作　　者：Yao Jin Qi Liu Chuhang Zhou Shidi Han Yuanhang Zhou Xinping Hu Leqi Wang Yan Liu 靳尧;刘琦;周楚杭;韩诗迪;周远航;胡新平;王乐淇;刘艳(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)

机构地区：[1]Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

出　　处：《Journal of Chinese Pharmaceutical Sciences》2019年第8期561-570,共10页中国药学（英文版）

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

摘　　要：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 Pep T1-targeted polymeric micelles were prepared and characterized. The structure of the synthesized Gly-Sar-PEG-b-PLA was confirmed by use of TLC and 1 H-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.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：Intestinal transporter Oligopeptide transporter PepT1 Gly-Sar Polymeric micelles Oral administration 

分 类 号：R943[医药卫生—药剂学]