Drug Delivery (Dec 2023)

Folic acid-modified reverse micelle-lipid nanocapsules overcome intestinal barriers and improve the oral delivery of peptides

  • Jibiao He,
  • Ruihuan Ding,
  • Yuping Tao,
  • Zhenyu Zhao,
  • Ranran Yuan,
  • Houqian Zhang,
  • Aiping Wang,
  • Kaoxiang Sun,
  • Youxin Li,
  • Yanan Shi

DOI
https://doi.org/10.1080/10717544.2023.2181744
Journal volume & issue
Vol. 30, no. 1

Abstract

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AbstractThe oral absorption of exenatide, a type 2 diabetes medication, can be increased by employing lipid nanocapsules (LNC). To increase mucus permeability and exenatide intestinal absorption, reverse micelle lipid nanocapsules (RM-LNC) were prepared and their surface was modified with DSPE-PEG-FA. The RM-LNC with surface modification of DSPE-PEG-FA (FA-RM-LNC) were able to target enterocytes and reduce mucus aggregation in the intestine. Furthermore, in vitro absorption at different intestinal sites and flip-flop intestinal loop experiments revealed that LNCs with surface modification significantly increased their absorption efficiency in the small intestine. FA-RM-LNC delivers more drugs into Caco-2 cells via caveolin-, macrophagocytosis-, and lipid raft-mediated endocytosis. Additionally, the enhanced transport capacity of FA-RM-LNC was observed in a study of monolayer transport in Caco-2 cells. The oral administration of exenatide FA-RM-LNC resulted in a prolonged duration of hypoglycemia in diabetic mice and a relative bioavailability (BR) of up to 7.5% in rats. In conclusion, FA-RM-LNC can target enterocytes and has promising potential as a nanocarrier for the oral delivery of peptides.

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