BiomaterialsOct 23, 2017

Nanoparticles use the bile acid route to cross intestinal barriers for oral insulin delivery

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 26, 2026

Abstract

Oral bioavailability of insulin delivered via deoxycholic acid-modified nanoparticles is 15.9% in type I diabetic rats.

Deoxycholic acid-conjugated chitosan nanoparticles (DNPs) are designed to enhance oral absorption of protein drugs.
DNPs utilize the bile acid pathway to effectively overcome intestinal barriers, including mucus and cell membranes.
Internalization of DNPs occurs through a specific transporter (ASBT), facilitating their uptake by intestinal cells.
DNPs prevent insulin degradation by escaping from the endolysosomal system within epithelial cells.
Intracellular transport and release of insulin are aided by interaction between DNPs and a cytosolic bile acid-binding protein.

Simplified

Oral absorption of protein/peptide-loaded nanoparticles is often limited by multiple barriers of the intestinal epithelium. In addition to mucus translocation and apical endocytosis, highly efficient transepithelial absorption of nanoparticles requires successful intracellular trafficking, especially to avoid lysosomal degradation, and basolateral release. Here, the functional material, deoxycholic acid-conjugated chitosan, is synthesized and loaded with the model protein drug insulin into deoxycholic acid-modified nanoparticles (DNPs). The DNPs designed in this study are demonstrated to overcome multiple barriers of the intestinal epithelium by exploiting the bile acid pathway. In Caco-2 cell monolayers, DNPs are internalized via apical sodium-dependent bile acid transporter (ASBT)-mediated endocytosis. Interestingly, insulin degradation in the epithelium is significantly prevented due to endolysosomal escape of DNPs. Additionally, DNPs can interact with a cytosolic ileal bile acid-binding protein that facilitates the intracellular trafficking and basolateral release of insulin. In rats, intravital two-photon microscopy also reveals that the transport of DNPs into the intestinal villi is mediated by ASBT. Further pharmacokinetic studies disclose an oral bioavailability of 15.9% in type I diabetic rats after loading freeze-dried DNPs into enteric-coated capsules. Thus, deoxycholic acid-modified chitosan nanoparticles can overcome multiple barriers of the intestinal epithelium for oral delivery of insulin.

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Nanoparticles use the bile acid route to cross intestinal barriers for oral insulin delivery

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