Nanotechnology and material surface modification have provided a functional platform for the advancement of several medical fields such as dermatology. Furthermore, the smart choice of preparation material was proven to confer unique properties to the develbped nanosystems. In this context, we focused on the sphingolipid "cer-amide", whose deficiency was found to negatively affect psoriasis. Ceramide was doped into surfactant based vesicular.phospholipid systems to create tubulated vesicles "cerosomes" loaded with a model anti-psoriatic drug "tazarotene", and their properties were tested as compared to ceramide free vesicles. Cerosomes were characterized for their drug entrapment, viscosity, in vitro drug release, morphology, ex vivo drug skin deposition, thermal behavior, and were clinically tested on psoriatic patients. The factorial design study revealed that the surfactant type, the ceramide: surfactant ratio, and the presence of ethanol in the hydration buffer affected the entrapment efficiency and the viscosity of the vesicles. Ceramide increased the entrapment of tazarotene, decreased its release while enhancing its deposition within the skin, correlating with better clinical therapeutic outcome compared to the topical marketed product. Ceramide was also able to cause significant membrane tubulation in the vesicles, causing them to deviate from the conventional spherical morphology. As a conclusion, cerosomes present a new functional treatment modality for psoriasis which is worthy of future experimentation.(C) 2017 Elsevier B.V. All rights reserved.