224 Skin layers targeting by multi-lamellar liposomes; interest for drug delivery in atopic dermatitis

Abstract

In the frame of atopic dermatitis (AD), epidermis restricted delivery of corticosteroids represents a promising strategy for drug efficiency improvement, blood transfer diminution and therefore side effects decrease. Multi-lamellar liposomes (MLLs) of controlled size, charge and elasticity are good candidates to reach such purposes. Their good entrapment efficiency of hydrophilic and hydrophobic molecules and the ability of plain MLLs to remain in chosen skin layers has been demonstrated on Strat-M™ (an artificial skin model) and dog skin. In this study, we demonstrated that after corticosteroid encapsulation we are still able to control MLLs physico-chemical properties and target epidermal layer on the Strat-M™ model. Using Franz cell, 33 % of free corticosteroid crossed the Strat-M™ after 48 h against less than 2 % for the encapsulated form. Using skin explants, we showed that plain and corticosteroid-loaded MLLs did not alter skin architecture, and confirmed that encapsulation decreased the transdermal passage of corticosteroids. Existing models of reconstructed epidermis for atopic dermatitis are made on polycarbonate filter and thus lack dermis. To evaluate the targeting efficiency of MLLs, we developed a new model on dead deepidermized dermis. After 48h exposure to cytokines (Il-4, IL-13, IL-17), our model showed an increased epidermal thickness, a decrease in filaggrin, loricrin staining, and an increase in carbonic anhydrase 2 staining which are the main characteristics of AD. Thus, this new model is suitable to test the ability of the corticosteroid-loaded MLLs to reverse cytokines-induced epidermal alteration.