The dorsal skinfold chamber : A valuable model for the in vivo evaluation of topical formulations

Abstract

In this study, we introduce the mouse dorsal skinfold chamber model as a valuable approach for the in vivo evaluation of topical formulations. For this purpose, dorsal skinfold chambers were implanted into BALB/c mice. Tumor necrosis factor (TNF)‐α was administered to the chamber tissue for the local induction of inflammation fol‐ lowed by the application of diclofenac‐containing or diclofenac‐free (control) gel onto the skin of the chamber backside. Intravital fluorescence microscopy was repetitively performed throughout an observation period of 24 hours to study macromolecular leakage, leucocyte‐endothelial cell interactions and microhaemodynamic parameters. In addition, infiltration of the inflamed tissue with different immune cell subtypes was assessed by immunohistochemistry. In a second set of experiments, the effect of dermal application of a diclofenac‐containing gel on photochemically induced throm‐ bus formation was analysed. It was observed that macromolecular leakage, numbers of adherent leucocytes and tissue infiltrating myeloperoxidase (MPO)‐positive neu‐ trophilic granulocytes and CD68‐positive macrophages were significantly reduced in dorsal skinfold chambers treated with diclofenac‐containing gel when compared to controls. Moreover, the diclofenac‐containing gel exerted an anti‐thrombotic activ‐ ity, as indicated by a significantly prolonged complete vessel occlusion time. These findings demonstrate that the mouse dorsal skinfold chamber represents a valid and versatile tool to evaluate the effects of topical formulations in vivo.