Amelioration of Imiquimod-induced Psoriasis in the Mice model by Topical Delivery of Phosphodiesterase 4 Inhibitor Roflumilast Incorporated Nanoemulgel

Abstract

Several clinical trials on repurposing of roflumilast are in progress, majorly focused on the potential treatment for psoriasis and atopic dermatitis like inflammatory skin diseases. Therefore, the current research focuses on formulation and in vivo evaluation of repurposed drug roflumilast loaded nanoemulgel for topical management of psoriasis. The roflumilast loaded nanoemulsion was prepared by spontaneous nanoemulsification method. The optimized roflumilast nanoemulsion has shown droplet size of found to be 10.92 ± 0.15 nm, PDI <0.3. The optimized nanoemulsion was further converted into gel referred as nanoemulgel. The prepared nanoemulgel has shown pseudoplastic shear thinning behaviour with pH value ranging between the skin pH while the content of roflumilast (%) was found >95%. Ex vivo permeation study of roflumilast nanoemulgel showed significantly higher skin retention of roflumilast (**p < 0.01) compared to free roflumilast gel. The antipsoriatic potential of roflumilast nanomulgel has been evaluated in psoriasis model of BALB/c mice. The levels of pro-inflammatory cytokines including IL-17, IL-22, IL-23 and TNF-α in skin homogenates of mice group treated with roflumilast nanoemulgel showed significant reduction compared to negative control. Furthermore, the histopathology of mice skin treated with topical roflumilast nanoemulgel showed reduced psoriatic lesions. The study findings clearly demonstrated the effectiveness roflumilast loaded nanoemulgel (0.1% w/w) for the topical management of psoriasis in mice.

Keywords: Imiquimod; Nanoemulgel; Phosphodiesterase-4 inhibitors; Psoriasis; Roflumilast.