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.