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• W3197671491 abstract "Despite many ongoing and innovative approaches, there are still formidable challenges in the clinical translation of oral peptide drugs into marketable products due to their low absorption and poor bioavailability. Herein, a novel nanocarrier platform was developed that employs a hydrophobic ion-pairing (HIP) of model peptide (insulin) and the anionic bile salt (sodium glycodeoxycholate, SGDC), and markedly improves intestinal absorption via the bile acid pathway. The developed HIP-nanocomplexes (C1 and C2) were optimized, characterized, and in vitro and in vivo evaluation were performed to assess oral efficacy of these system. The optimal molar ratios of C1 and C2-nanocomplexes were 30:1 and 6:1 (SGDC:insulin), respectively. Compared to the insulin solution, the C1 and C2 nanocomplexes significantly enhanced the permeation of insulin across the Caco-2 cell monolayers, with 6.36- and 4.05-fold increases in apparent permeability, respectively. Uptake mechanism studies were conducted using different endocytosis inhibitors and apical sodium-dependent bile acid transporter (ASBT)-transfected MDCK cells, which demonstrated the involvement of the energy-dependent ASBT-mediated active transport. Furthermore, the intrajejunal administration of C1 and C2 resulted in their pharmacological availabilities (PA) being 6.44% and 0.10%, respectively, indicating increased potential for C1, when compared to C2. Similarly, the PA and the relative bioavailability with intrajejunal administration of the C1 were 17.89-fold and 16.82-fold greater than those with intracolonic administration, respectively, confirming better jejunal absorption of C1. Overall, these findings indicate that the HIP-nanocomplexes could be a prominent platform for the effective delivery of peptides with improved intestinal absorption." @default.
• W3197671491 created "2021-09-13" @default.
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• W3197671491 date "2021-10-01" @default.
• W3197671491 modified "2023-10-14" @default.
• W3197671491 title "Bile acid transporter-mediated oral absorption of insulin via hydrophobic ion-pairing approach" @default.
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• W3197671491 doi "https://doi.org/10.1016/j.jconrel.2021.08.060" @default.
• W3197671491 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34481926" @default.
• W3197671491 hasPublicationYear "2021" @default.
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