Abstract
Psoriasis is an inflammatory skin disease characterized by the presence of whitish and scaly plaques, which can cover up to 90% of the body surface. These plaques result from the hyperproliferation and abnormal differentiation of keratinocytes. Dermopharmaceutical testing of new therapies is limited by healthy and pathological skin models, which are not closely enough mimicking their in vivo counterparts. In this study, we exploited percutaneous absorption and Ultra Performance Liquid Chromatography (UPLC) analyses in order to determine the metabolic capacity of our psoriatic skin model. Skin substitutes were reconstructed according to the self-assembly method and tested regarding their percutaneous absorption of a topical formulation of tazarotene, followed by UPLC analyses. Histological and immunofluorescence analyses confirmed both the healthy and psoriatic phenotypes. Results from percutaneous absorption showed a significant level of tazarotene metabolite (tazarotenic acid) when the formulation was applied over 24 h on the skin substitutes. The presence of tazarotenic acid in the dermis and the epidermis of healthy and psoriatic skin substitutes confirms the metabolic capacity of both skin models, and thereby their ability to screen new molecules with antipsoriatic potential. In conclusion, the present data suggest that our psoriatic skin model could possibly be used in clinic to screen in vitro responses of patient to a panel of drugs without having them experiencing the drawback of each drug.
Highlights
Psoriasis is a chronic inflammatory disease which affects 2 to 3% of the world population, both men and women [1]. It is characterized by the presence of whitish and scaly plaques that can be found on every body part [2]. Those plaques are the result of the abnormal differentiation and hyperproliferation of keratinocytes, which leads to a thicker epidermis [3,4,5]
Morphology of the Psoriatic Skin Substitutes Produced by Tissue Engineering
Macroscopic analyses showed that healthy substitutes (HS) (Figure 2a) had a regular aspect on the majority of the sample surface, with a smooth and uniform aspect, suggesting a normal epidermal differentiation and a normal distribution all over the surface
Summary
Psoriasis is a chronic inflammatory disease which affects 2 to 3% of the world population, both men and women [1] It is characterized by the presence of whitish and scaly plaques that can be found on every body part [2]. Psoriasis is characterized by the infiltration of immune cells, increased angiogenesis, and the retention of nuclei by corneocytes (parakeratosis) [6,7] In this pathology many genes have their expression modified, including differentiation, proliferation, and inflammation markers. Detailed knowledge of this help researchers to ensure that psoriatic skin substitutes represent a good model for molecule screening metabolism could help researchers to ensure that psoriatic skin substitutes represent a good model open the door to and moreopen personalized medicine. Normal human skin (NHS), healthy substitutes (HS), and psoriatic tazarotene. To tazarotene quantify the amount of tazarotene and itsacid) metabolite
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