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Apremilast Microemulsion as Topical Therapy for Local Inflammation: Design, Characterization and Efficacy Evaluation
Apremilast (APR) is a selective phosphodiesterase 4 inhibitor administered orally in the treatment of moderate-to-severe plaque psoriasis and active psoriatic arthritis. The low solubility and permeability of this drug hinder its dermal administration. The purpose of this study was to design and cha...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767333/ https://www.ncbi.nlm.nih.gov/pubmed/33371334 http://dx.doi.org/10.3390/ph13120484 |
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author | Sarango-Granda, Paulo Silva-Abreu, Marcelle Calpena, Ana Cristina Halbaut, Lyda Fábrega, María-José Rodríguez-Lagunas, María J. Díaz-Garrido, Natalia Badia, Josefa Espinoza, Lupe Carolina |
author_facet | Sarango-Granda, Paulo Silva-Abreu, Marcelle Calpena, Ana Cristina Halbaut, Lyda Fábrega, María-José Rodríguez-Lagunas, María J. Díaz-Garrido, Natalia Badia, Josefa Espinoza, Lupe Carolina |
author_sort | Sarango-Granda, Paulo |
collection | PubMed |
description | Apremilast (APR) is a selective phosphodiesterase 4 inhibitor administered orally in the treatment of moderate-to-severe plaque psoriasis and active psoriatic arthritis. The low solubility and permeability of this drug hinder its dermal administration. The purpose of this study was to design and characterize an apremilast-loaded microemulsion (APR-ME) as topical therapy for local skin inflammation. Its composition was determined using pseudo-ternary diagrams. Physical, chemical and biopharmaceutical characterization were performed. Stability of this formulation was studied for 90 days. Tolerability of APR-ME was evaluated in healthy volunteers while its anti-inflammatory potential was studied using in vitro and in vivo models. A homogeneous formulation with Newtonian behavior and droplets of nanometric size and spherical shape was obtained. APR-ME released the incorporated drug following a first-order kinetic and facilitated drug retention into the skin, ensuring a local effect. Anti-inflammatory potential was observed for its ability to decrease the production of IL-6 and IL-8 in the in vitro model. This effect was confirmed in the in vivo model histologically by reduction in infiltration of inflammatory cells and immunologically by decrease of inflammatory cytokines IL-8, IL-17A and TNFα. Consequently, these results suggest that this formulation could be used as an attractive topical treatment for skin inflammation. |
format | Online Article Text |
id | pubmed-7767333 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-77673332020-12-28 Apremilast Microemulsion as Topical Therapy for Local Inflammation: Design, Characterization and Efficacy Evaluation Sarango-Granda, Paulo Silva-Abreu, Marcelle Calpena, Ana Cristina Halbaut, Lyda Fábrega, María-José Rodríguez-Lagunas, María J. Díaz-Garrido, Natalia Badia, Josefa Espinoza, Lupe Carolina Pharmaceuticals (Basel) Article Apremilast (APR) is a selective phosphodiesterase 4 inhibitor administered orally in the treatment of moderate-to-severe plaque psoriasis and active psoriatic arthritis. The low solubility and permeability of this drug hinder its dermal administration. The purpose of this study was to design and characterize an apremilast-loaded microemulsion (APR-ME) as topical therapy for local skin inflammation. Its composition was determined using pseudo-ternary diagrams. Physical, chemical and biopharmaceutical characterization were performed. Stability of this formulation was studied for 90 days. Tolerability of APR-ME was evaluated in healthy volunteers while its anti-inflammatory potential was studied using in vitro and in vivo models. A homogeneous formulation with Newtonian behavior and droplets of nanometric size and spherical shape was obtained. APR-ME released the incorporated drug following a first-order kinetic and facilitated drug retention into the skin, ensuring a local effect. Anti-inflammatory potential was observed for its ability to decrease the production of IL-6 and IL-8 in the in vitro model. This effect was confirmed in the in vivo model histologically by reduction in infiltration of inflammatory cells and immunologically by decrease of inflammatory cytokines IL-8, IL-17A and TNFα. Consequently, these results suggest that this formulation could be used as an attractive topical treatment for skin inflammation. MDPI 2020-12-21 /pmc/articles/PMC7767333/ /pubmed/33371334 http://dx.doi.org/10.3390/ph13120484 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sarango-Granda, Paulo Silva-Abreu, Marcelle Calpena, Ana Cristina Halbaut, Lyda Fábrega, María-José Rodríguez-Lagunas, María J. Díaz-Garrido, Natalia Badia, Josefa Espinoza, Lupe Carolina Apremilast Microemulsion as Topical Therapy for Local Inflammation: Design, Characterization and Efficacy Evaluation |
title | Apremilast Microemulsion as Topical Therapy for Local Inflammation: Design, Characterization and Efficacy Evaluation |
title_full | Apremilast Microemulsion as Topical Therapy for Local Inflammation: Design, Characterization and Efficacy Evaluation |
title_fullStr | Apremilast Microemulsion as Topical Therapy for Local Inflammation: Design, Characterization and Efficacy Evaluation |
title_full_unstemmed | Apremilast Microemulsion as Topical Therapy for Local Inflammation: Design, Characterization and Efficacy Evaluation |
title_short | Apremilast Microemulsion as Topical Therapy for Local Inflammation: Design, Characterization and Efficacy Evaluation |
title_sort | apremilast microemulsion as topical therapy for local inflammation: design, characterization and efficacy evaluation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767333/ https://www.ncbi.nlm.nih.gov/pubmed/33371334 http://dx.doi.org/10.3390/ph13120484 |
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