Angubindin-1, a novel paracellular absorption enhancer acting at the tricellular tight junction

Journal of Controlled Release : Official Journal of the Controlled Release Society
Susanne M KrugMasuo Kondoh

Abstract

A limiting barrier for mucosal absorption of drugs is the tight junction (TJ). TJs exist between two adjacent cells (bicellular TJ, bTJ) and at the sites where three cells meet (tricellular TJ, tTJ). We present a novel approach which employs a physiologically regulated pathway for the passage of large molecules through the tTJ. Main barrier-relevant tTJ proteins are tricellulin and angulin-1 to -3. We developed an angulin binder from Clostridium perfringens iota-toxin (Ib) whose receptor is angulin-1. An Ib fragment corresponding to amino acids 421-664 (Ib421-664) of iota-toxin proved to bind in cells expressing angulin-1 and -3, but not angulin-2. This binding led to removal of angulin-1 and tricellulin from the tTJ which enhanced the permeation of macromolecular solutes. Ib421-664 enhanced intestinal absorption in rats and mice. Our findings indicate that Ib421-664, which we designate angubindin-1, is a modulator of the tTJ barrier and that modulation of that barrier qualifies for a new strategy of developing a mucosal absorption enhancer.

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Citations

Aug 21, 2019·International Journal of Molecular Sciences·Yosuke HashimotoMasuo Kondoh
Jul 2, 2020·Archives of Physiology and Biochemistry·Bo ZhaoYunman Li
Nov 20, 2019·International Journal of Molecular Sciences·Carlos Ayala-TorresMichael Fromm
Oct 12, 2019·Nature Reviews. Cancer·Costas D ArvanitisRakesh K Jain
Dec 10, 2019·Biochimica Et Biophysica Acta. Biomembranes·Tomohito Higashi, Hideki Chiba
Feb 23, 2021·Advanced Drug Delivery Reviews·Joël BrunnerGerrit Borchard
Mar 24, 2020·Pharmacology & Therapeutics·Akira YamamotoHidemasa Katsumi
May 1, 2020·Biochimica Et Biophysica Acta. Biomembranes·Yosuke Hashimoto, Matthew Campbell
Mar 27, 2021·International Journal of Biological Macromolecules·Cameron WellsLezanne Ooi
Sep 9, 2018·Journal of Controlled Release : Official Journal of the Controlled Release Society·Khaled AlmansourRandall J Mrsny
Apr 30, 2021·Journal of Cell Science·Mariana Castro DiasBritta Engelhardt
May 23, 2020·Drug Discovery Today·Yosuke HashimotoMasuo Kondoh
Aug 8, 2021·International Journal of Molecular Sciences·Carlos Ayala-TorresMichael Fromm
Aug 18, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Takayuki KohnoTakashi Kojima
Aug 20, 2021·Advanced Drug Delivery Reviews·Yuandong ZhangXun Sun
Aug 28, 2021·International Journal of Molecular Sciences·Kizuku OhwadaTakashi Kojima

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