A Novel Topical Nitric Oxide Releasing Gel Demonstrates Effective Nail Penetration and Potent Antifungal Activity in Onychomycosis

Abstract

Introduction:

Onychomycosis remains a difficult-to-treat fungal infection due to nail plate impermeability, high recurrence, and limited efficacy of topical agents. Systemic antifungals are effective but constrained by safety and drug interaction concerns. Nitric oxide (NO), a small antimicrobial molecule, may overcome these barriers through superior penetration and broad fungicidal activity.

Aim:

To evaluate the nail penetration, antifungal efficacy, and early clinical potential of a nitric oxide–releasing gel (NORS-Gel) in onychomycosis.

Methods:

Ex vivo human nail models were used to assess NORS-Gel penetration and antifungal activity with colorimetric, immunohistochemical, and microbiological assays. Comparative assays with terbinafine were conducted. Two patients with culture-confirmed or clinically diagnosed onychomycosis applied NORS-Gel daily for 4–6 weeks, with safety and early outcomes recorded.

Results:

NORS-Gel fully penetrated the nail plate, confirmed by s-nitrosothiol accumulation and nail discoloration. Fungal burden assays showed complete eradication of Trichophyton mentagrophytes (0 CFU/g) versus terbinafine (3.58 ± 0.2 log₁₀ CFU/g). In an ex vivo infection model, NORS-Gel achieved full clearance within 14 days, sustained through Day 30, with no regrowth during 21-day post-treatment incubation. In observational human cases, NORS-Gel was well tolerated, with only transient nail discoloration and occasional mild local irritation. Non-great toenails showed early evidence of healthy regrowth; follow-up was insufficient to confirm great toenail outcomes.

Conclusions:

NORS-Gel achieves rapid and complete nail penetration and demonstrates potent fungicidal activity in ex vivo models. Early clinical experience supports its safety and potential efficacy. Controlled clinical trials are warranted to validate findings and establish treatment protocols.

Sponsored: SaNOtize Research and Development Corporation