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Int. J. Mol. Sci. 2017, 18(12), 2548; doi:10.3390/ijms18122548

Human Skin Permeation Studies with PPARγ Agonist to Improve Its Permeability and Efficacy in Inflammatory Processes

Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain
Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, 08028 Barcelona, Spain
Departamento de Química y Ciencias Exactas, Universidad Técnica Particular de Loja, Loja 1101608, Ecuador
Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain
Institut de Recerca en Nutrició i Seguretat Alimentària (INSA), Universitat de Barcelona (UB), 08028 Barcelona, Spain
Institute of Biomedicine, University of Barcelona, 08028 Barcelona, Spain
Author to whom correspondence should be addressed.
Received: 30 October 2017 / Revised: 17 November 2017 / Accepted: 21 November 2017 / Published: 28 November 2017
(This article belongs to the Special Issue Inflammatory Skin Conditions 2017)
View Full-Text   |   Download PDF [2373 KB, uploaded 28 November 2017]   |  


Rosacea is the most common inflammatory skin disease. It is characterized by erythema, inflammatory papules and pustules, visible blood vessels, and telangiectasia. The current treatment has limitations and unsatisfactory results. Pioglitazone (PGZ) is an agonist of peroxisome proliferator-activated receptors (PPARs), a nuclear receptor that regulates important cellular functions, including inflammatory responses. The purpose of this study was to evaluate the permeation of PGZ with a selection of penetration enhancers and to analyze its effectiveness for treating rosacea. The high-performance liquid chromatography (HPLC) method was validated for the quantitative determination of PGZ. Ex vivo permeation experiments were realized in Franz diffusion cells using human skin, in which PGZ with different penetration enhancers were assayed. The results showed that the limonene was the most effective penetration enhancer that promotes the permeation of PGZ through the skin. The cytotoxicity studies and the Draize test detected cell viability and the absence of skin irritation, respectively. The determination of the skin color using a skin colorimetric probe and the results of histopathological studies confirmed the ability of PGZ-limonene to reduce erythema and vasodilation. This study suggests new pharmacological indications of PGZ and its possible application in the treatment of skin diseases, namely rosacea. View Full-Text
Keywords: skin permeation; PPAR-γ; pioglitazone; limonene; rosacea; inflammation skin permeation; PPAR-γ; pioglitazone; limonene; rosacea; inflammation

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Silva-Abreu, M.; Espinoza, L.C.; Rodríguez-Lagunas, M.J.; Fábrega, M.-J.; Espina, M.; García, M.L.; Calpena, A.C. Human Skin Permeation Studies with PPARγ Agonist to Improve Its Permeability and Efficacy in Inflammatory Processes. Int. J. Mol. Sci. 2017, 18, 2548.

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