Addressing filamentous fungi-related onychomycosis in the era of antifungal resistance: assessment of Zataria multiflora nanostructured lipid carrier topical gel in a double-blinded clinical trial

Background and Purpose: Onychomycosis, a prevalent fungal infection affecting the nails, presents considerable difficulties in clinical treatment. Zataria multiflora (Zat), with its known antifungal properties, presents a promising approach for treatment. The present study focused on the evaluation of the effectiveness of Zat-NLC ۱% gel against mold-associated onychomycosis, compared to a placebo.Materials and Methods: The Zat-loaded nanostructured lipid carriers (Zat-NLCs) were prepared and optimized by utilizing an ultrasonic probe approach. Antifungal susceptibility testing followed Clinical and Laboratory Standards Institute M۳۸-A۳ guidelines on the most common dermatophytes and non-dermatophytes fungal species. A double-blind trial with ۴۰ participants (۲۰ volunteers from each gender, equally divided into two groups, namely Zat-NLCs ۱% gel and placebo receivers) evaluated Zat-NLC ۱% gel efficacy. Causative agents were identified at the species level using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.Results: A mono-dispersed suspension of spherical nanoparticles with zeta potential, Z-average, and polydispersity index of -۲۶.۶±۷.۷ mV, ۲۷۳.۹±۳ nm, and ۰.۳۶۹±۰.۰۳, respectively, was achieved with no cytotoxicity. The Zat-NLCs demonstrated a significant inhibitory effect on both dermatophytes and non-dermatophyte fungal growth, in vitro. Effective improvement was observed in mycological criteria, compared to the placebo group (P<۰.۰۰۵) after ۲ weeks of treatment. The mycological cure rate was ۷۰% for Zat-NLCs gel after only ۲ weeks. The results were notably different from those observed in the placebo group following the same duration of application (۷۰% vs. ۵۵%). However, the difference was insignificant in the mentioned groups after ۴ weeks of application due to the prescription of routine antifungals for onychomycosis. The PCR-RFLP outputs revealed T. mentagrophytes/interdigitale complex and A. section Flavi as the predominant isolated species of dermatophytes and non-dermatophytes, respectively.Conclusion: Nanoscale colloidal systems loading with antifungals might be strongly considered a better and more efficient cure for mold-related dermatophytosis.

Keywords:

Clinical trials , Onychomycosis , Filamentous fungi , Nanostructured lipid carrier , Zataria multiflora