Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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
_version_ 1783628934099763200
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
work_keys_str_mv AT sarangograndapaulo apremilastmicroemulsionastopicaltherapyforlocalinflammationdesigncharacterizationandefficacyevaluation
AT silvaabreumarcelle apremilastmicroemulsionastopicaltherapyforlocalinflammationdesigncharacterizationandefficacyevaluation
AT calpenaanacristina apremilastmicroemulsionastopicaltherapyforlocalinflammationdesigncharacterizationandefficacyevaluation
AT halbautlyda apremilastmicroemulsionastopicaltherapyforlocalinflammationdesigncharacterizationandefficacyevaluation
AT fabregamariajose apremilastmicroemulsionastopicaltherapyforlocalinflammationdesigncharacterizationandefficacyevaluation
AT rodriguezlagunasmariaj apremilastmicroemulsionastopicaltherapyforlocalinflammationdesigncharacterizationandefficacyevaluation
AT diazgarridonatalia apremilastmicroemulsionastopicaltherapyforlocalinflammationdesigncharacterizationandefficacyevaluation
AT badiajosefa apremilastmicroemulsionastopicaltherapyforlocalinflammationdesigncharacterizationandefficacyevaluation
AT espinozalupecarolina apremilastmicroemulsionastopicaltherapyforlocalinflammationdesigncharacterizationandefficacyevaluation