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Ethosomal Gel for Topical Administration of Dimethyl Fumarate in the Treatment of HSV-1 Infections

The infections caused by the HSV-1 virus induce lesions on the lips, mouth, face, and eye. In this study, an ethosome gel loaded with dimethyl fumarate was investigated as a possible approach to treat HSV-1 infections. A formulative study was conducted, evaluating the effect of drug concentration on...

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Autores principales: Sicurella, Mariaconcetta, Pula, Walter, Musiał, Karolina, Cieślik-Boczula, Katarzyna, Sguizzato, Maddalena, Bondi, Agnese, Drechsler, Markus, Montesi, Leda, Esposito, Elisabetta, Marconi, Peggy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9967198/
https://www.ncbi.nlm.nih.gov/pubmed/36835541
http://dx.doi.org/10.3390/ijms24044133
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author Sicurella, Mariaconcetta
Pula, Walter
Musiał, Karolina
Cieślik-Boczula, Katarzyna
Sguizzato, Maddalena
Bondi, Agnese
Drechsler, Markus
Montesi, Leda
Esposito, Elisabetta
Marconi, Peggy
author_facet Sicurella, Mariaconcetta
Pula, Walter
Musiał, Karolina
Cieślik-Boczula, Katarzyna
Sguizzato, Maddalena
Bondi, Agnese
Drechsler, Markus
Montesi, Leda
Esposito, Elisabetta
Marconi, Peggy
author_sort Sicurella, Mariaconcetta
collection PubMed
description The infections caused by the HSV-1 virus induce lesions on the lips, mouth, face, and eye. In this study, an ethosome gel loaded with dimethyl fumarate was investigated as a possible approach to treat HSV-1 infections. A formulative study was conducted, evaluating the effect of drug concentration on size distribution and dimensional stability of ethosomes by photon correlation spectroscopy. Ethosome morphology was investigated by cryogenic transmission electron microscopy, while the interaction between dimethyl fumarate and vesicles, and the drug entrapment capacity were respectively evaluated by FTIR and HPLC. To favor the topical application of ethosomes on mucosa and skin, different semisolid forms, based on xanthan gum or poloxamer 407, were designed and compared for spreadability and leakage. Dimethyl fumarate release and diffusion kinetics were evaluated in vitro by Franz cells. The antiviral activity against HSV-1 was tested by plaque reduction assay in Vero and HRPE monolayer cells, while skin irritation effect was evaluated by patch test on 20 healthy volunteers. The lower drug concentration was selected, resulting in smaller and longer stable vesicles, mainly characterized by a multilamellar organization. Dimethyl fumarate entrapment in ethosome was 91% w/w, suggesting an almost total recovery of the drug in the lipid phase. Xanthan gum 0.5%, selected to thicken the ethosome dispersion, allowed to control drug release and diffusion. The antiviral effect of dimethyl fumarate loaded in ethosome gel was demonstrated by a reduction in viral growth both 1 h and 4 h post-infection. Moreover, the patch test demonstrated the safety of the ethosomal gel applied on the skin.
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spelling pubmed-99671982023-02-26 Ethosomal Gel for Topical Administration of Dimethyl Fumarate in the Treatment of HSV-1 Infections Sicurella, Mariaconcetta Pula, Walter Musiał, Karolina Cieślik-Boczula, Katarzyna Sguizzato, Maddalena Bondi, Agnese Drechsler, Markus Montesi, Leda Esposito, Elisabetta Marconi, Peggy Int J Mol Sci Article The infections caused by the HSV-1 virus induce lesions on the lips, mouth, face, and eye. In this study, an ethosome gel loaded with dimethyl fumarate was investigated as a possible approach to treat HSV-1 infections. A formulative study was conducted, evaluating the effect of drug concentration on size distribution and dimensional stability of ethosomes by photon correlation spectroscopy. Ethosome morphology was investigated by cryogenic transmission electron microscopy, while the interaction between dimethyl fumarate and vesicles, and the drug entrapment capacity were respectively evaluated by FTIR and HPLC. To favor the topical application of ethosomes on mucosa and skin, different semisolid forms, based on xanthan gum or poloxamer 407, were designed and compared for spreadability and leakage. Dimethyl fumarate release and diffusion kinetics were evaluated in vitro by Franz cells. The antiviral activity against HSV-1 was tested by plaque reduction assay in Vero and HRPE monolayer cells, while skin irritation effect was evaluated by patch test on 20 healthy volunteers. The lower drug concentration was selected, resulting in smaller and longer stable vesicles, mainly characterized by a multilamellar organization. Dimethyl fumarate entrapment in ethosome was 91% w/w, suggesting an almost total recovery of the drug in the lipid phase. Xanthan gum 0.5%, selected to thicken the ethosome dispersion, allowed to control drug release and diffusion. The antiviral effect of dimethyl fumarate loaded in ethosome gel was demonstrated by a reduction in viral growth both 1 h and 4 h post-infection. Moreover, the patch test demonstrated the safety of the ethosomal gel applied on the skin. MDPI 2023-02-18 /pmc/articles/PMC9967198/ /pubmed/36835541 http://dx.doi.org/10.3390/ijms24044133 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sicurella, Mariaconcetta
Pula, Walter
Musiał, Karolina
Cieślik-Boczula, Katarzyna
Sguizzato, Maddalena
Bondi, Agnese
Drechsler, Markus
Montesi, Leda
Esposito, Elisabetta
Marconi, Peggy
Ethosomal Gel for Topical Administration of Dimethyl Fumarate in the Treatment of HSV-1 Infections
title Ethosomal Gel for Topical Administration of Dimethyl Fumarate in the Treatment of HSV-1 Infections
title_full Ethosomal Gel for Topical Administration of Dimethyl Fumarate in the Treatment of HSV-1 Infections
title_fullStr Ethosomal Gel for Topical Administration of Dimethyl Fumarate in the Treatment of HSV-1 Infections
title_full_unstemmed Ethosomal Gel for Topical Administration of Dimethyl Fumarate in the Treatment of HSV-1 Infections
title_short Ethosomal Gel for Topical Administration of Dimethyl Fumarate in the Treatment of HSV-1 Infections
title_sort ethosomal gel for topical administration of dimethyl fumarate in the treatment of hsv-1 infections
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9967198/
https://www.ncbi.nlm.nih.gov/pubmed/36835541
http://dx.doi.org/10.3390/ijms24044133
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