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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-12-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/13/12/484 |
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| author | Paulo Sarango-Granda Marcelle Silva-Abreu Ana Cristina Calpena Lyda Halbaut María-José Fábrega María J. Rodríguez-Lagunas Natalia Díaz-Garrido Josefa Badia Lupe Carolina Espinoza |
| author_facet | Paulo Sarango-Granda Marcelle Silva-Abreu Ana Cristina Calpena Lyda Halbaut María-José Fábrega María J. Rodríguez-Lagunas Natalia Díaz-Garrido Josefa Badia Lupe Carolina Espinoza |
| author_sort | Paulo Sarango-Granda |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T13:53:43Z |
| format | Article |
| id | doaj.art-c66cb5421e9144ce8df93acfef4d823e |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T13:53:43Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-c66cb5421e9144ce8df93acfef4d823e2023-11-21T01:53:37ZengMDPI AGPharmaceuticals1424-82472020-12-01131248410.3390/ph13120484Apremilast Microemulsion as Topical Therapy for Local Inflammation: Design, Characterization and Efficacy EvaluationPaulo Sarango-Granda0Marcelle Silva-Abreu1Ana Cristina Calpena2Lyda Halbaut3María-José Fábrega4María J. Rodríguez-Lagunas5Natalia Díaz-Garrido6Josefa Badia7Lupe Carolina Espinoza8Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, SpainDepartment of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, SpainDepartment of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, SpainDepartment of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, SpainDepartment of Experimental and Health Sciences, Parc de Recerca Biomèdica de Barcelona, University Pompeu Fabra (UPF), 08005 Barcelona, SpainDepartment of Biochemistry and Physiology, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, SpainDepartment of Biochemistry and Physiology, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, SpainDepartment of Biochemistry and Physiology, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, SpainDepartment of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, SpainApremilast (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.https://www.mdpi.com/1424-8247/13/12/484apremilastphosphodiesterase 4microemulsionskin diseasesinflammation |
| spellingShingle | Paulo Sarango-Granda Marcelle Silva-Abreu Ana Cristina Calpena Lyda Halbaut María-José Fábrega María J. Rodríguez-Lagunas Natalia Díaz-Garrido Josefa Badia Lupe Carolina Espinoza Apremilast Microemulsion as Topical Therapy for Local Inflammation: Design, Characterization and Efficacy Evaluation Pharmaceuticals apremilast phosphodiesterase 4 microemulsion skin diseases inflammation |
| 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 | apremilast phosphodiesterase 4 microemulsion skin diseases inflammation |
| url | https://www.mdpi.com/1424-8247/13/12/484 |
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