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Autors principals: Rodrigues-Braz, Daniela, Linxin, Zhu, Clarin, Jean-Pierre, Gélizé, Emmanuelle, Chatagnon, Xavier, Benzine, Youcef, Rampignon, Philippe, Thouvenin, Agathe, Bourges, Jean-Louis, Behar-Cohen, Francine, Zhao, Min
Format: Recurso digital
Idioma:anglès
Publicat: Zenodo 2024
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Accés en línia:https://doi.org/10.3390/ph16101446
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author Rodrigues-Braz, Daniela
Linxin, Zhu
Clarin, Jean-Pierre
Gélizé, Emmanuelle
Chatagnon, Xavier
Benzine, Youcef
Rampignon, Philippe
Thouvenin, Agathe
Bourges, Jean-Louis
Behar-Cohen, Francine
Zhao, Min
author_facet Rodrigues-Braz, Daniela
Linxin, Zhu
Clarin, Jean-Pierre
Gélizé, Emmanuelle
Chatagnon, Xavier
Benzine, Youcef
Rampignon, Philippe
Thouvenin, Agathe
Bourges, Jean-Louis
Behar-Cohen, Francine
Zhao, Min
contents <p>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.</p>
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spellingShingle Spironolactone Eyedrop Favors Restoration of Corneal Integrity after Wound Healing in the Rat
Rodrigues-Braz, Daniela
Linxin, Zhu
Clarin, Jean-Pierre
Gélizé, Emmanuelle
Chatagnon, Xavier
Benzine, Youcef
Rampignon, Philippe
Thouvenin, Agathe
Bourges, Jean-Louis
Behar-Cohen, Francine
Zhao, Min
spironolactone
drug development
topical administration
eyedrop
corneal wound healing
ocular surface
cornea
<p>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.</p>
title Spironolactone Eyedrop Favors Restoration of Corneal Integrity after Wound Healing in the Rat
topic spironolactone
drug development
topical administration
eyedrop
corneal wound healing
ocular surface
cornea
url https://doi.org/10.3390/ph16101446