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

doi:10.5246/jcps.2019.08.054

Journal of Chinese Pharmaceutical Sciences ›› 2019, Vol. 28 ›› Issue (8): 561-570.DOI: 10.5246/jcps.2019.08.054

• Original articles • Previous Articles Next Articles

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^*

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).

Abstract

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

CLC Number:

R943

Supporting:

Yao Jin, Qi Liu, Chuhang Zhou, Shidi Han, Yuanhang Zhou, Xinping Hu, Leqi Wang, Yan Liu. Construction and characterization of intestinal oligopeptide transporter PepT1-targeted polymeric micelles for enhanced intestinal absorption of poorly water-soluble agents[J]. Journal of Chinese Pharmaceutical Sciences, 2019, 28(8): 561-570.

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

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