Polypeptide-corticosteroid conjugates as a topical treatment approach to psoriasis.

Fecha de publicación: 01/02/2020 Fecha Ahead of Print: 14/12/2019

Autores de IIS La Fe

María Dolores Pérez Del Caz

Autor

Participantes ajenos a IIS La Fe

Dolz-Pérez I
Sallam MA
Masiá E
Morelló-Bolumar D
Graff P
Abdelmonsif D
Hedtrich S
Nebot VJ
Vicent MJ

Grupos

Dermatología y Regeneración Tisular

Leader

Rafael Botella Estrada

Abstract

Topical treatment of mild-to-moderate psoriasis with corticosteroids suffers from challenges that include reduced drug bioavailability at the desired site of action. The retention of therapeutics within the epidermis can safely treat skin inflammation, scaling, and erythema associated with psoriasis while avoiding possible side effects associated with systemic treatments. We successfully synthesized and characterized a pH-responsive biodegradable poly-L-glutamic acid (PGA)-fluocinolone acetonide (FLUO) conjugate that allows the controlled release of the FLUO to reduce skin inflammation. Additionally, the application of a hyaluronic acid (HA)-poly-L-glutamate cross polymer (HA-CP) vehicle boosted skin permeation. During in vitro and ex vivo analyses, we discovered that PGA-FLUO inhibited pro-inflammatory cytokine release, suggesting that polypeptidic conjugation fails to affect the anti-inflammatory activity of FLUO. Additionally, ex vivo human skin permeation studies using confocal microscopy revealed the presence of PGA-FLUO within the epidermis, but a minimal presence in the dermis, thereby reducing the likelihood of FLUO entering the systemic circulation. Finally, we demonstrated that PGA-FLUO applied within HA-CP effectively reduced psoriasis-associated phenotypes in an in vivo mouse model of human psoriasis while also lowering levels of pro-inflammatory cytokines in tissue and serum. Overall, our experimental results demonstrate that PGA-FLUO within an HA-CP penetration enhancer represents an effective topical treatment for psoriasis.

Datos de la publicación

ISSN/ISSNe:: 0168-3659, 1873-4995
Tipo:: Article
Páginas:: 210-222
DOI:: 10.1016/j.jconrel.2019.12.016
Factor de Impacto:: 2,119 SCImago ℠
Cuartil:: Q1 SCImago ℠

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Métricas

Filiaciones

Dolz-Pérez I:: Polymer Therapeutics Laboratory, Centro de Investigación Príncipe Felipe, Av. Eduardo Primo Yúfera 3, Valencia 46012, Spain
Sallam MA:: Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, El Sultan Hussein St Azarita, Egypt

John A. Paulson school of engineering and applied sciences and Wyss institute for biologically inspired engineering, Harvard University, 52 Oxford St, Cambridge, MA 02138, USA
Masiá E:: Polymer Therapeutics Laboratory, Centro de Investigación Príncipe Felipe, Av. Eduardo Primo Yúfera 3, Valencia 46012, Spain

Screening Platform, Centro de Investigación Príncipe Felipe, Av. Eduardo Primo Yúfera 3, Valencia 46012, Spain
Morelló-Bolumar D:: Polypeptide Therapeutic Solutions S.L. C/ Benjamin Franklin 19 (Paterna), Valencia 46980, Spain
Pérez Del Caz MD:: Servicio de cirugía plástica, Hospital Universitario y Politécnico La Fe, Av. de Fernando Abril Martorell 106, Valencia 46026, Spain
Graff P:: Institute of Pharmacy (Pharmacology and Toxicology), Freie Universität Berlin, Königin-Luise Str. 2+4, Berlin 14195, Germany
Abdelmonsif D:: Department of Medical Biochemistry, Faculty of Medicine, Alexandria University, El Sultan Hussein St Azarita, Egypt
Hedtrich S:: Institute of Pharmacy (Pharmacology and Toxicology), Freie Universität Berlin, Königin-Luise Str. 2+4, Berlin 14195, Germany

Faculty of Pharmaceutical Sciences, University of British Columbia, 2405 Wesbrook Mall, Vancouver, BC, Canada
Nebot VJ:: Polypeptide Therapeutic Solutions S.L. C/ Benjamin Franklin 19 (Paterna), Valencia 46980, Spain
Vicent MJ:: Polymer Therapeutics Laboratory, Centro de Investigación Príncipe Felipe, Av. Eduardo Primo Yúfera 3, Valencia 46012, Spain

Screening Platform, Centro de Investigación Príncipe Felipe, Av. Eduardo Primo Yúfera 3, Valencia 46012, Spain