Efficacy of Apremilast Gels in Mouse Model of Imiquimod-Induced Psoriasis Skin Inflammation
Marcelle Silva-Abreu,
Lilian Sosa,
Lupe Carolina Espinoza,
María-José Fábrega,
María J. Rodríguez-Lagunas,
Mireia Mallandrich,
Ana Cristina Calpena,
María Luisa Garduño-Ramírez,
María Rincón
Affiliations
Marcelle Silva-Abreu
Departament de Farmàcia, Tecnologia Farmacèutica, i Fisicoquímica, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona (UB), 08028 Barcelona, Spain
Lilian Sosa
Research Institute of Applied Sciences and Technology, National Autonomous University of Honduras (UNAH), Tegucigalpa 11101, Honduras
Lupe Carolina Espinoza
Institut de Nanociència i Nanotecnologia IN2UB, University of Barcelona, 08028 Barcelona, Spain
María-José Fábrega
Department of Experimental and Health Sciences, Parc de Recerca Biomèdica de Barcelona, University Pompeu Fabra (UPF), 08005 Barcelona, Spain
María J. Rodríguez-Lagunas
Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain
Mireia Mallandrich
Departament de Farmàcia, Tecnologia Farmacèutica, i Fisicoquímica, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona (UB), 08028 Barcelona, Spain
Ana Cristina Calpena
Departament de Farmàcia, Tecnologia Farmacèutica, i Fisicoquímica, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona (UB), 08028 Barcelona, Spain
María Luisa Garduño-Ramírez
Center for Chemical Research, Institute for Research Basic and Applied Sciences, Autonomous University of the State of Morelos, Av. Universidad 1001, Cuernavaca 62209, Mexico
María Rincón
Institut de Nanociència i Nanotecnologia IN2UB, University of Barcelona, 08028 Barcelona, Spain
Apremilast (APM) is a novel drug for the treatment of psoriasis and psoriatic arthritis. APM is a phosphodiesterase 4 (PDE4) inhibitor, raising intracellular cAMP levels and thereby decreasing the inflammatory response by modulating the expression of TNF-α, IL-17, IL-23, and other inflammatory cytokines. The goal of this study is to develop APM gels as a new pharmaceutical formulation for the treatment of topical psoriasis. APM was solubilized in Transcutol-P and incorporated into Pluronic F127, Sepigel, and carbomer bases at different proportions. All formulations were characterized physiochemically. A biopharmaceutical study (release profile) was performed, and ex vivo permeation was evaluated using a human skin model. A toxicity assay was carried out on the HaCaT cell line. A mouse model of imiquimod-induced psoriasis skin inflammation was carried out to determine its efficacy by histological analysis, RNA extraction, and RT-qPCR assays. APM gel formulations showed good physicochemical characteristics and a sustained release profile. There was no permeation of any gel measured through human skin, indicating a high retained amount of APM on the skin. Cell viability was greater than 80% at most dilution concentrations. APM gels treated the psoriasis mouse model, and it shows a reduction in the proinflammatory cytokines (IL-8, IL-17A, IL-17F, and IL-23). APM gels could be a new approach for the treatment of topical psoriasis.
