Ruxolitinib phosphate-laden nanoemulgel: amelioration of ex vivo permeation and in vivo therapeutic efficacy for the effective therapeutic management of psoriasis

Psoriasis is a chronic, immune-driven inflammatory skin ailment marked by recurrent flare-ups. Ongoing clinical investigations are focused on therapeutic strategies that modulate key signaling pathways implicated in disease pathogenesis. Ruxolitinib (RUX) is a Janus kinase 1/2 inhibitor approved for several hematological and inflammatory disorders, is being clinically investigated as a potential therapeutic option for psoriasis. The current study reports the formulation, characterization, and assessment of in vitro, ex vivo, and in vivo efficacy of RUX-loaded nanoemulgel (RUX NEG) for the management of psoriasis. The spontaneous emulsification method was employed to prepare RUX-loaded nanoemulsion, which has shown a droplet size of 50.35 ± 1.05 nm with a polydispersity index of 0.20 ± 0.01. Further, RUX-loaded nanoemulsion incorporated in a gel matrix to form a RUX-NEG that has shown pseudoplastic shear thinning behaviour. Meanwhile, ex vivo permeation of RUX-NEG demonstrated steady-state flux and significantly higher retention (74.12 ± 13.56 µg/g) of RUX in epidermal skin layers than that of plain gel (52.39 ± 8.69 µg/cm²/h). Moreover, in vivo therapeutic efficacy was evaluated in an imiquimod-induced psoriasis model in mice, which revealed that RUX-NEG significantly attenuated the severity index score and psoriasis area, as well as inflammatory cytokine levels such as IL-17, IL-22, and IL-23, by 3.82-, 2.29-, and 2.71-fold compared with the negative control. Histopathological changes also confirmed improvement in skin condition after treatment with the RUX-NEG formulation compared with the negative control. These findings concluded potential improvement in the anti-inflammatory activity of RUX after loading into nanoemulgel for the effective management of psoriasis.