The effect of gastro-intestinal mucus on drug absorption

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 trac