Evaluation of mucosal damage and recovery in the gastrointestinal tract of rats by penetration enhancers

Improving oral absorption of poorly absorbed drugs has always been a major focus in drug delivery research. When poor intestinal epithelial permeability is associated with high polarity or low water solubility, absorption promoters could be used to overcome epithelial absorption barrier. Penetration enhancers have been studied for almost five decades to improve oral drug absorption. Two important aspects of studies involving penetration enhancers are evaluation of efficacy and safety. Many studies have established the efficacy of penetration enhancers in causing drug absorption enhancement. But, safety has always been a concern with penetration enhancers. The possibility of increasing absorption of toxic substances especially the endogenous endotoxins due to the local action of penetration enhancers has deterred the regulatory bodies from approving them for human use.; In this study, we have attempted to address this issue by evaluating kinetics of mucosal recovery by measuring absorption of poorly absorbed markers and morphological changes. We developed a pharmacokinetic tool to evaluate functional recovery of gastrointestinal mucosa dynamically, after administration of a penetration enhancer. We found that it is possible to achieve absorption enhancement with temporary and reversible alteration of mucosal barrier properties. The changes noted in absorption of marker molecules as a result of treatment with a penetration enhancer and the subsequent recovery were in accordance with morphological changes observed using microscopy techniques. After treatment with a penetration enhancer for 14 days, no permanent changes in absorption kinetics and morphology were observed. These results hopefully will help to improve the design of future studies involving the use of penetration enhancers and in a better understanding of their effects on the mucosal membrane.