Abstract
The first step in drug absorption is the passage of drug molecules across epithelial cell sheets. Epithelial cell sheets are pivotal for the maintenance of homeostasis in the body by acting as a biological barrier that separates the inside of the body from the outside environment. Intercellular space between the adjacent epithelial cells is tightly sealed by tight junctions (TJs), which prevent solutes from freely moving across the epithelial cell sheets. Modulation of the TJ barrier has been a potent strategy for drug absorption. Absorption enhancers have been investigated since the 1980s, and sodium caprate is clinically used as an absorption enhancer. However, the biochemical constituents and structures of TJs were not elucidated until 1993. Occludin, a tetra-transmembrane protein, was identified to be a structural component of TJs in 1993. Claudin, another tetra-transmembrane protein, was identified as a structural and functional component of TJs in 1998. Modulation of occludin- or claudin-barrier is novel methods to enhance drug absorption. Recently, synthetic TJbinding peptides, a kinase of claudin and peptide fragments of toxins have been developed. In the present review, we summarize the recent progress in TJ-modulating peptides and discuss their potencies.
Keywords: Tight junction, occludin, claudin, drug absorption, Clostridium perfringens enterotoxin (CPE), dextran, amino acids, pro-inflammatory cytokine, VP8, Zonula occludens toxin (Zot)
Current Pharmaceutical Design
Title: Peptides as Tight Junction Modulators
Volume: 17 Issue: 25
Author(s): Azusa Takahashi, Masuo Kondoh, Miki Kodaka and Kiyohito Yagi
Affiliation:
Keywords: Tight junction, occludin, claudin, drug absorption, Clostridium perfringens enterotoxin (CPE), dextran, amino acids, pro-inflammatory cytokine, VP8, Zonula occludens toxin (Zot)
Abstract: The first step in drug absorption is the passage of drug molecules across epithelial cell sheets. Epithelial cell sheets are pivotal for the maintenance of homeostasis in the body by acting as a biological barrier that separates the inside of the body from the outside environment. Intercellular space between the adjacent epithelial cells is tightly sealed by tight junctions (TJs), which prevent solutes from freely moving across the epithelial cell sheets. Modulation of the TJ barrier has been a potent strategy for drug absorption. Absorption enhancers have been investigated since the 1980s, and sodium caprate is clinically used as an absorption enhancer. However, the biochemical constituents and structures of TJs were not elucidated until 1993. Occludin, a tetra-transmembrane protein, was identified to be a structural component of TJs in 1993. Claudin, another tetra-transmembrane protein, was identified as a structural and functional component of TJs in 1998. Modulation of occludin- or claudin-barrier is novel methods to enhance drug absorption. Recently, synthetic TJbinding peptides, a kinase of claudin and peptide fragments of toxins have been developed. In the present review, we summarize the recent progress in TJ-modulating peptides and discuss their potencies.
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Cite this article as:
Takahashi Azusa, Kondoh Masuo, Kodaka Miki and Yagi Kiyohito, Peptides as Tight Junction Modulators, Current Pharmaceutical Design 2011; 17 (25) . https://dx.doi.org/10.2174/138161211797416084
DOI https://dx.doi.org/10.2174/138161211797416084 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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