# Novel Nitric Oxide-Releasing Formulations Show Fungicidal Potential for Superficial Dermatophyte Infection

## TL;DR

Nitric oxide-releasing gels and solutions show promise in fighting fungal skin infections like athlete's foot.

## Contribution

A NO-releasing gel (NORG) is proposed as a new formulation with rapid fungicidal activity and good skin penetration.

## Key findings

- NORG showed rapid fungicidal activity against T. rubrum and T. mentagrophytes.
- NORS treatment reduced clinical symptom severity by 67% with no significant safety issues.
- Fungal cell damage observed suggests potential fungicidal activity of NO formulations.

## Abstract

A commercially available nitric oxide (NO)-releasing solution (NORS) has demonstrated in vitro efficacy for dermatophytosis, but a NO-releasing gel (NORG) may be more suitable for patient self-application. We present a preliminary investigation of NORS for tinea pedis and an in vitro investigation of NORG for dermatophyte infection, to complement the existing published data and expand support for a possible role of NO formulations in superficial dermatophyte infection. In vitro usage of NORS and NORG is reviewed. The antifungal efficacy of NORG was assessed via time-kill assays, zone of inhibition tests with synthetic dermal membrane permeation, and scanning electron microscopy. A randomized, controlled pilot study of NORS for tinea pedis investigated the safety and efficacy of treatment over three consecutive days, with a day-31 follow-up. The NORG demonstrated rapid fungicidal activity against T. rubrum and T. mentagrophytes and effective dermal membrane penetration while retaining antifungal action. Significant morphological damage to fungal cells was noted, indicating possible fungicidal activity. The clinical NORS treatment reduced the clinical symptom severity score by 67% on average, with no significant safety findings. These findings, in addition to existing publications, support NO-releasing formulations as potential therapies that warrant further clinical investigation for superficial fungal infection.