RESUMO
Recent data suggest that apart from its well-known role in the regulation of xenobiotic metabolizing enzymes, AhR is also involved in inflammation. However, the influence of inflammation on AhR expression remains unknown. Here, we demonstrated that proinflammatory conditions induced by either PMA or IL-1 ß enhance AhR expression in Caco-2 cells. This was associated with an increase in AhR promoter activity. By means of directed mutagenesis experiments and the use of proteasome inhibitors, we demonstrated that inflammation-induced AhR expression involved the NF κ B pathway but not AP-1. Moreover, conditioned media from PMA-treated Caco-2 cells were also able to induce AhR expression, and this induction was repressed by anti-IL-1 ß blocking antibodies. Similar results were obtained with conditioned media from PMA-treated THP-1 cells. Taken together, these data suggest that AhR could be involved in vivo in an inflammatory loop. AhR was recently suspected to be implicated in inflammatory bowel disease. Our results support this hypothesis and suggest that AhR could be a new target for inflammatory bowel disease patient management.
RESUMO
Over the years, different formulation technologies intended for gastro retentive dosage delivery were investigated and patented. The aim of this study was to develop an innovative floating gastro retentive dosage form (GRDF). The developed technology induces a low-density dosage form containing high active pharmaceutical ingredient (API) concentration by using a hydrophobic dusty powder excipient under specific conditions. The new dosage form was obtained by state of the art wet granulation manufacturing process. An experimental design using a discrete variable and four mixture variables was conducted in order to optimize API concentration and buoyancy of the new dosage form. An apparatus was developed to measure the apparent density of floating tablet. The GRDF was characterized for apparent density, buoyancy, porosity and dissolution using in vitro experimentations.