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Spironolactone Eyedrop Favors Restoration of Corneal Integrity after Wound Healing in the Rat

Abnormal corneal wound healing can compromise corneal transparency and lead to visual impairment. Mineralocorticoid receptor antagonists (MRA) are promising candidates to promote corneal remodeling with anti-inflammatory properties and lack gluococorticoids-associated side effects. In this preclinic...

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Autores principales: Rodrigues-Braz, Daniela, Zhu, Linxin, Gélizé, Emmanuelle, Clarin, Jean-Pierre, Chatagnon, Xavier, Benzine, Youcef, Rampignon, Philippe, Thouvenin, Agathe, Bourges, Jean-Louis, Behar-Cohen, Francine, Zhao, Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10609951/
https://www.ncbi.nlm.nih.gov/pubmed/37895917
http://dx.doi.org/10.3390/ph16101446
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author Rodrigues-Braz, Daniela
Zhu, Linxin
Gélizé, Emmanuelle
Clarin, Jean-Pierre
Chatagnon, Xavier
Benzine, Youcef
Rampignon, Philippe
Thouvenin, Agathe
Bourges, Jean-Louis
Behar-Cohen, Francine
Zhao, Min
author_facet Rodrigues-Braz, Daniela
Zhu, Linxin
Gélizé, Emmanuelle
Clarin, Jean-Pierre
Chatagnon, Xavier
Benzine, Youcef
Rampignon, Philippe
Thouvenin, Agathe
Bourges, Jean-Louis
Behar-Cohen, Francine
Zhao, Min
author_sort Rodrigues-Braz, Daniela
collection PubMed
description Abnormal corneal wound healing can compromise corneal transparency and lead to visual impairment. Mineralocorticoid receptor antagonists (MRA) are promising candidates to promote corneal remodeling with anti-inflammatory properties and lack gluococorticoids-associated side effects. In this preclinical study, a new polymer-free hydroxypropyl-gamma-cyclodextrin-based eyedrop containing 0.1% spironolactone (SPL), a potent but non-water-soluble MRA, was investigated for its ocular surface tolerance and efficacy in a rat model of corneal wound healing. SPL eyedrops were stable for up to 9 months at 4 °C. The formulation was well-tolerated since no morphological changes or inflammatory reactions were observed in the rat cornea after multiple daily instillations over 7 days. SPL eyedrops accelerated rat corneal wound healing, reduced corneal edema and inflammation, enhanced epithelial integrity, and improved nerve regeneration, suggesting restoration of corneal homeostasis, while potassium canrenoate, an active and soluble metabolite of SPL, had no effect. SPL eyedrops could benefit patients with impaired corneal wound healing, including that secondary to glucocorticoid therapy. Repurposing known drugs with known excipients will expedite translation to the clinic.
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spelling pubmed-106099512023-10-28 Spironolactone Eyedrop Favors Restoration of Corneal Integrity after Wound Healing in the Rat Rodrigues-Braz, Daniela Zhu, Linxin Gélizé, Emmanuelle Clarin, Jean-Pierre Chatagnon, Xavier Benzine, Youcef Rampignon, Philippe Thouvenin, Agathe Bourges, Jean-Louis Behar-Cohen, Francine Zhao, Min Pharmaceuticals (Basel) Article Abnormal corneal wound healing can compromise corneal transparency and lead to visual impairment. Mineralocorticoid receptor antagonists (MRA) are promising candidates to promote corneal remodeling with anti-inflammatory properties and lack gluococorticoids-associated side effects. In this preclinical study, a new polymer-free hydroxypropyl-gamma-cyclodextrin-based eyedrop containing 0.1% spironolactone (SPL), a potent but non-water-soluble MRA, was investigated for its ocular surface tolerance and efficacy in a rat model of corneal wound healing. SPL eyedrops were stable for up to 9 months at 4 °C. The formulation was well-tolerated since no morphological changes or inflammatory reactions were observed in the rat cornea after multiple daily instillations over 7 days. SPL eyedrops accelerated rat corneal wound healing, reduced corneal edema and inflammation, enhanced epithelial integrity, and improved nerve regeneration, suggesting restoration of corneal homeostasis, while potassium canrenoate, an active and soluble metabolite of SPL, had no effect. SPL eyedrops could benefit patients with impaired corneal wound healing, including that secondary to glucocorticoid therapy. Repurposing known drugs with known excipients will expedite translation to the clinic. MDPI 2023-10-12 /pmc/articles/PMC10609951/ /pubmed/37895917 http://dx.doi.org/10.3390/ph16101446 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
Rodrigues-Braz, Daniela
Zhu, Linxin
Gélizé, Emmanuelle
Clarin, Jean-Pierre
Chatagnon, Xavier
Benzine, Youcef
Rampignon, Philippe
Thouvenin, Agathe
Bourges, Jean-Louis
Behar-Cohen, Francine
Zhao, Min
Spironolactone Eyedrop Favors Restoration of Corneal Integrity after Wound Healing in the Rat
title Spironolactone Eyedrop Favors Restoration of Corneal Integrity after Wound Healing in the Rat
title_full Spironolactone Eyedrop Favors Restoration of Corneal Integrity after Wound Healing in the Rat
title_fullStr Spironolactone Eyedrop Favors Restoration of Corneal Integrity after Wound Healing in the Rat
title_full_unstemmed Spironolactone Eyedrop Favors Restoration of Corneal Integrity after Wound Healing in the Rat
title_short Spironolactone Eyedrop Favors Restoration of Corneal Integrity after Wound Healing in the Rat
title_sort spironolactone eyedrop favors restoration of corneal integrity after wound healing in the rat
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10609951/
https://www.ncbi.nlm.nih.gov/pubmed/37895917
http://dx.doi.org/10.3390/ph16101446
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