Enhanced anti-psoriatic activity of tacrolimus loaded nanoemulsion gel via omega 3 - Fatty acid (EPA and DHA) rich oils-fish oil and linseed oil

Psoriasis is an autoimmune disease that affects around 3–4% of the population globally leading to skin inflammation. Tacrolimus is widely used in the treatment of psoriasis due to its ability to suppress inflammation and immune response. But formation of scaly plaques and dry patches are hurdle in delivering drug via topical route. The aim of present study was to develop, optimize and characterize tacrolimus loaded nanoemulsion gel to get enhanced anti-psoriatic activity. Nanoemulsion was prepared using spontaneous emulsification method combined with high pressure homogenization technique using fish oil and linseed oil (2 different oils), tween 80 (surfactant) and transcutol-P (co-surfactant). Fish oil and linseed oil were used as oil phase as they contain high amount of eicosapentaenoic acid and docosahexaenoic acid, and possess anti-inflammatory activity. The optimized nanoemulsions (fish oil an linseed oil containing nanoemulsions) attained using central composite rotable design had desired average hydrodynamic diameter (<130 nm) and narrow PDI along with high percentage transmittance (>95%). The optimized nanoemulsion was transformed into nanoemulsion gel using 1% carbopol-934. The cumulative drug permeated through the skin was 1.3 and 1.4-fold higher for nanoemulsion gel-F and L respectively compared to marketed ointment. The confocal laser scanning microscopy and dermatokinetic studies confirmed enhanced depth of permeation and skin retention (~1.5-folds) for developed nanoemulsion gel. In vivo study performed on mice using Imiquimod induced psoriasis-like inflammation model, showed significantly high anti-psoriatic activity in mice treated with nanoemulsion gels compared to marketed ointment. Significant reduction in the levels of cytokines (TNF-α and IL-6) in the skin, showed promising outcome in the treatment of psoriasis, of developed nanoemulsion gels compared to marketed ointment. Thus, it was concluded that fish oil and linseed oil integrated tacrolimus nanoemulsion gel could improve the efficacy of tacrolimus and is a promising carrier in the treatment of psoriasis.