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Psoriasis is a widespread chronic disease affecting 2–4% of the population in Western countries. Its mild-to-moderate form, representing approximately 80% of the total cases, is treated by topical application, with corticosteroid being the standard treatment. However, in case of psoriasis, no single treatment works for every patient and optimizing topical therapy is a key aspect. A possible alternative is represented by cyclosporine, an immunosuppressant cyclic peptide administered orally in the treatment of the severe form. Its topical application could avoid the problems related to systemic immunosuppression, but the unfavourable physico-chemical properties (MW: 1202Da; LogP≈3) hinder its permeation across the stratum corneum. The aim of the paper was the preparation, characterization and ex-vivo evaluation of cyclosporine loaded microemulsions using oleic acid as oil phase, either Tween®80 or a soluble derivative of vitamin E (TPGS) as surfactants and either Transcutol®, propylene glycol or 1,3 propanediol as co-surfactants. The issue of formulation viscosity was also addressed 1) by evaluating the thickening of Tween®80-based microemulsions by direct addition of different rheological modifiers, 2) by building pseudo-ternary phase diagrams using TPGS, to identify the water/oil/surfactants proportions resulting in viscous self-gelifying systems. Nine formulations (five Tween®80-based and four TPGS-based) were selected, characterized in terms of droplets size (low viscosity systems) or rheological properties (high viscosity systems), loaded with 6mg/g cyclosporine and applied ex-vivo on porcine skin for 22h. A relevant skin accumulation was obtained either with a low-viscosity Tween®80-based microemulsion (9.78±3.86μg/cm2), or with a high viscosity TPGS-based microemulsion (18.3±5.69μg/cm2), with an increase of about 3 and 6 times respectively for comparison with a control cyclosporine solution in propylene glycol. The role of water content, surfactant, co-surfactant and viscosity was also addressed and discussed. The kinetic of skin uptake from the best performing formulation was finally evaluated, highlighting a relatively quick skin uptake and the achievement, after 2h of contact, of potentially therapeutic cyclosporine skin concentrations.