Coencapsulation of Immunosuppressive Drug with Anti-Inflammatory Molecule in Pickering Emulsions as an Innovative Therapeutic Approach for Inflammatory Dermatoses

Psoriasis is an inflammatory skin disease characterized by epidermal and immune dysfunctions. Although efficient, current topical treatments display adverse effects, including skin atrophy and burning sensation, leading to poor patient adherence. To overcome these downsides, Pickering emulsions were formulated in which the calcitriol-containing dispersed phase was stabilized with either cyclosporin A- or tacrolimus-loaded PLGA nanoparticles. This study aimed to investigate their biological effects on lymphocytes and epidermal cells and their effectiveness in an imiquimod-induce psoriasis-like mouse model. Results showed that both emulsions significantly inhibited NFAT translocation in T lymphocytes as well as their IL-2 production, cell activation and proliferation. In keratinocytes, inhibition of NFAT translocation decreased the production of IL-8 and TNF-α. Topical application of emulsions over skin biopsies ex vivo showed accumulation of rhodamin B-coupled PLGA nanoparticles throughout the epidermis by immunofluorescence and significantly decreased the antigen-presenting capacity of Langerhans cells in relation with a reduced expression of activation markers CD40, CD86 and HLA-DR. Using an imiquimod-induced psoriasis model in vivo, Pickering emulsions significantly alleviated psoriasiform lesions potentially attributed to the decreased cutaneous expression of T cell markers, pro-inflammatory cytokines, chemokines and specific epidermal cell genes. Altogether, Pickering emulsions might be a very efficient formulation for treating inflammatory dermatoses.