Enhanced oral drug delivery by mimicking natural amino acid and oligopeptide absorption route  

作　　者：Ruinan Wu Xiaoxing Fan Licheng Wu Liyun Xing Jinxia Kong Zhou Zhou Jingyuan Wen Lian Li Yuan Huang 

机构地区：[1]Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province,Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology,West China School of Pharmacy,Sichuan University,Chengdu 610041,China [2]School of Pharmacy,Faculty of Medical and Health Sciences,University of Auckland,Auckland 1023,New Zealand

出　　处：《Nano Research》2025年第2期525-540,共16页纳米研究(英文版)

基　　金：This work was supported by the National Key Research and Development Program of China(No.2021YFE0115200);the Regional Innovation and Development Joint Fund of National Natural Science Foundation of China(No.U22A20356).

摘　　要：Oral delivery of protein and peptide drugs presents considerable challenges due to their susceptibility to digestive enzymes in gastrointestinal(Gl)tract and low efficiency of transepithelial transport.Herein,inspired by efficient absorption of protein-based nutrients,we constructed several kinds of oral drug delivery systems by mimicking natural amino acid and oligopeptide absorption route.Three kinds of amino acids and two kinds of oligopeptides were chosen as targeting ligands to mediate transportation of orally administered nanoparticles(NPs).Liraglutide(Lira),a kind of glucagon like peptide-1(GLP-1)receptor agonist,was used as model drug.These functionalized NPs could protect Lira from enzymatic degradation in Gl tract.Moreover,compared with amino acid-modified NPs,oligopeptide-modified NPs exhibited greater transepithelial transport efficiency and were primarily absorbed in the proximal small intestine due to the high expression and transportation mediated by proton coupled oligopeptide transporter 1(PEPT1).These Lira-loaded NPs could effectively control the blood glucose level,reduce plasma lipid level,and repair tissue damage on type 2 diabetic mice and even showed comparable hypoglycemic effects of subcutaneous injection(s.c.)free Lira.Our study demonstrates the potential of mimicking natural oligopeptide absorption route to enhance oral delivery of protein and peptide drugs.

关 键 词：oral drug delivery amino acid absorption route oligopeptide absorption route LIRAGLUTIDE 

分 类 号：O62[理学—有机化学]