The effect of gastro-intestinal mucus on drug absorption

doi:10.1016/0169-409X(93)90010-2

Advanced Drug Delivery Reviews

Volume 11, Issue 3, September 1993, Pages 201-220

https://doi.org/10.1016/0169-409X(93)90010-2 Get rights and content

Abstract

The layer of mucus covering the gastro-intestinal tract has a number of important functions. For example, it provides an unstirred buffering layer adjacent to the mucosal epithelium which protects the underlying membrane from the corrosive elements in the luminal content. Also as a visco-elastic gel, it aids the passage of food over the epithelium, thereby limiting potential erosive damage. The mucus layer is composed mainly of water, but it is the high-molecular-weight glycoprotein component which is responsible for gel formation. Differences in glycoprotein structure can impart varying properties to the mucus gel and attempts have been made to characterise mucus, especially changes which occur in disease states, by both histological and biochemical means. The mucus layer in addition to affording protection is also a potential barrier to drug absorption. Mucus has been shown to retard the diffusion of hydrogen ions when compared with an equivalent thickness of water. Specific drugs have been demonstrated to bind to mucus glycoprotein, thereby reducing the diffusion coefficient. There has been much current interest in the use of bioadhesive formulations and specific binding ligands with the view to decreasing the distance a drug must diffuse through the luminal contents in order to reach the mucosal epithelium. The high rates of mucus turnover may limit the exploitation of such devices within the gastro-intestinal tract.

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The effect of gastro-intestinal mucus on drug absorption

Abstract

Gastroenterology

Gastroenterology

Gastroenterology

Trends Biol. Sci. May

Comp. Biochem. Physiol.

Adv. Carbohydr. Chem. Biochem.

Int. J. Macromol.

Biochim. Biophys. Acta

Gastroenterology

Anal. Biochem.

Int. J. Pharm.

Gastroenterology

Gastroenterology

J. Theor. Biol.

Int. J. Pharm.

Biochem. Biophys. Res. Commun.

Int. J. Pharm.

Int. J. Pharm.

Biochem. Biophys. Res. Commun.

Gastric HCO3− secretion in the guinea pig

Am. J. Physiol.

Active alkalinization by amphibian gastric fundic mucosa in vitro

Am. J. Physiol.

Demonstration of a pH gradient across mucus adherent to rabbit gastric mucosa; evidence for a “mucus-bicarbonate” barrier

Gut

Demonstration of a pH gradient across the mucus layer of the surface of human gastric mucosa in vitro

Gut

Structure and function of gastrointestinal mucus

Mucus glycoprotein structure, gel formation and gastrointestinal mucus function

A simple method for measuring the thickness of the mucus gel layer adherent to rat, frog and human gastric mucosa: influence of feeding, prostaglandin, N-acetylcysteine and other agents

Clin. Sci.

Luminal mucin in the large intestine of mice, rats and guinea pigs

Cell Tissue Res.

Microbial flora of the mouse ileum mucous layer and epithelial surface

Appl. Environ. Microbiol.

Delineation of the dimensions and permeability characteristics of the two major diffusion barriers to passive mucosal uptake in the rabbit intestine

J. Clin. Invest.

Intestinal diffusion barrier: unstirred water layer or membrane surface water coat?

Science

The Influence of Intestinal Mucus on Drug Absorption

Dependence of hydrochloric acid diffusion through gastric mucus: correlation with diffusion through a water layer using a membrane mounted glass pH electrode

Analyst

Constituents of mucus and their separation

Br. Med. Bull.

The viscoelasticity of mucus: a molecular molecule

Progress Report: mucus and bicarbonate secretion in the stomach and their possible role in mucosal protection

Gut

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Biorheology

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Adv. Exp. Med. Biol.

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The biochemical and histochemical nomenclature of mucus

Br. Med. Bull.

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Biochem. J.

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Chemical aspects of mucus

Br. Med. Bull.

The effect of drugs on the structure and secretion of mucus

Pharm. Int.

Gastrointestinal mucus

Isolation and structural analysis of rat gastric mucus glycoprotein suggests a homogeneous protein backbone

Biochem. J.

Structure of gastro-intestinal mucus glycoproteins and the viscous and gel-forming properties of mucus

Br. Med. Bull.

Neutral and acidic species of human intestinal mucin

J. Biol. Chem.

Mucous glycoproteins: a gel of a problem

Essays Biochem.

Gastric HCO₃⁻ secretion in the guinea pig