ABSTRACT
The use of penetration enhancers and protease inhibitors is the most common approach to overcome various penetration and enzymatic barriers to mucosal drug absorption. In addition, formulation approach or a prodrug approach may also be feasible. Commonly used penetration enhancers include chelators, surfactants, bile salts, or fatty acids.5 The use of these
penetration enhancers may compromise the integrity of the mucosal membrane; thus, recovery of the mucosal damage is critical to the selection process. Penetration enhancers may promote drug absorption by the transcellular pathway (apical cell membrane) or the paracellular pathway (tight junction between cells). The paracellular pathway is gaining interest as it may lack proteolytic activity. The barrier to paracellular diffusion is a tight junction or zonula occludens. Use of a chelating agent to lower the extracellular Ca2+ concentration at this junction is known to enhance its permeability. The various protease inhibitors include the metalloprotease, aspartylprotease, cysteine proteinases, serine proteinase, aminopeptidase, or nonspecific inhibitors. Selection of which protease inhibitor to use will depend on the type of target protease and its subcellular distribution.6
