Methodology for assessing inflammatory induction potential of pharmaceutical adjuvants in the gastrointestine

摘要

Pharmaceutical adjuvants for enteric drug delviery such as absorption enhancers and surfactants should be nonirritative to the GI epithelium or minimal irritative, if at all. In addition to histology, biological assessments has recently been performed to evaluate the safety of adjuvants in an epithelial monolayer system. Proinflammatory mediators such as histamine, platelet activating factor and nitric oxide increase intestinal epithelial permeability and lead to the disruption its barrier function. Chemically-induced increase in the epithelial permeability could be mediated by stimulating the release of such a mediator from inflammatory cells in the lamina propria (Scheme 1). Nevertheless, the contribution of each mediator to mucosal hyperpermeability appears to be difficult to elucideate in vivo because each effects the blood vessels as well to cause an increase in endotherial permeability and blood flow. Hence, an in vitro methodology for evaluating the potential contribution of inflammatory mediators to chemically induced hyperpermeability of the intestinal mucosa due to pharmaceutical adjuvants has been established.