Nitric Oxide-Releasing Microparticles: A Novel Treatment for Onychomycosis

Onychomycosis is one of the most prevalent fungal infections worldwide, resulting in negative effects on general quality of life. Management of the disease encounters a series of obstacles, and antifungal treatment has a low success rate. We aimed to develop and evaluate a novel formulation of NO-releasing microparticles (SNO-MPs) against some of the most common causative agents of onychomycosis: Trichophyton mentagrophytes, Trichophyton rubrum, Candida albicans, and Aspergillus flavus. SNO-MP susceptibility testing was performed in vitro, and MICs and MFCs were established for multiple strains. SNO-MP was also tested ex vivo in human nail fragments, with biofilm formation and biofilm disruption assessed using scanning electron microscopy and colony-forming unit counting. The particles demonstrated the ability to destroy biofilms formed by either Trichophyton sp. or C. albicans. SNO-MP was not effective against A. flavus, which appears to have a nitrosative resistance mechanism that has not yet been elucidated. Cytotoxicity was assessed against human dermal fibroblasts and keratinocytes. SNO-MP demonstrated a manageable degree of cytotoxicity when tested against human dermal fibroblasts and keratinocytes. Our findings highlight that SNO-MP represents a potentially potent alternative for the treatment of onychomycosis due to Trichophyton and Candida.