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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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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. |
format | Online Article Text |
id | pubmed-10609951 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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