Nanocrystal-based gel of apremilast ameliorates imiquimod-induced psoriasis by suppressing inflammatory responses

[Display omitted] •Nanocrystal is a promising approach for ‘difficult-to-deliver’ drugs such as apremilast.•Nanocrystal-based gel enhanced the therapeutic efficacy of apremilast in the management of psoriasis.•Skin irritation study showed significantly less irritation potential of a nanocrystal-based gel than the positive control. Apremilast is ‘difficult-to-deliver’ in stratum corneum and viable layers (viable epidermis, dermis) owing to its modest lipophilicity and poor aqueous solubility, respectively. The objective of the present research was to develop apremilast nanocrystal-based gel for enhanced anti-psoriatic efficacy for the treatment of psoriasis. Nanosuspension was generated by wet media milling with a mean particle size of 200 nm. In-vivoefficacy of nanocrystal-based gels was evaluated in the imiquimod-induced psoriatic plaque model. Nanocrystal-based gel (1% and 3% w/w) improved phenotypic, histopathological features of psoriatic skin and attenuated splenic hypertrophy, psoriasis area severity scoring. Enzyme-linked immunosorbent assay was performed to evaluate levels of psoriatic biochemical markers indicating a significant decrease in the concentration of cytokines such as IL-23, IL-17A, IL-6 and TNF-α by nanocrystal-based gels (1% and 3% w/w) over disease induced group. Skin irritation study revealed that nanocrystal-based gel was significantly less irritating than the positive control. These results suggest that nanocrystal-based gel of apremilast can be an effective strategy for the management of psoriasis.