Ex vivo potential of a quinoline-derivative nail lacquer as a new alternative for dermatophytic onychomycosis treatment

Abstract

Introduction. Onychomycosis infections currently show a significant increase, affecting about 10 % of the world population. Trichophyton rubrum is the main agent responsible for about 80 % of the reported infections. The clinical cure for onychomycosis is extremely difficult and effective new antifungal therapy is needed. Hypothesis/Gap Statement. Ex vivo onychomycosis models using porcine hooves can be an excellent alternative for evaluating the efficacy of new anti-dermatophytic agents in a nail lacquer. Aim. Evaluation of the effectiveness of a nail lacquer containing a quinoline derivative on an ex vivo onychomycosis model using porcine hooves, as well as the proposal of a plausible antifungal mechanism of this derivative against dermatophytic strains. Methodology. The action mechanism of a quinoline derivative was evaluated through the sorbitol protection assay, exogenous ergosterol binding, and the determination of the dose-response curves by time-kill assay. Scanning electron microscopy evaluated the effect of the derivative in the fungal cells. The efficacy of a quinoline-derivative nail lacquer on an ex vivo onychomycosis model using porcine hooves was evaluated as well. Results. The quinoline derivative showed a time-dependent fungicidal effect, demonstrating reduction and damage in the morphology of dermatophytic hyphae. In addition, the ex vivo onychomycosis model was effective in the establishment of infection by T. rubrum. Conclusion. Treatment with the quinoline-derivative lacquer showed a significant inhibitory effect on T. rubrum strain in this infection model. Finally, the compound presents high potential for application in a formulation such as nail lacquer as a possible treatment for dermatophytic onychomycosis.

Development of a Clioquinol Nanocarrier as a New, Promising Option for the Treatment of Dermatomycosis

“…Nanoformulations containing CQ at MIC, MIC×2, MIC×4, and MIC×8 concentrations were prepared in RPMI 1640 medium and evaluated against Candida krusei (ATCC 6528) and a dermatophytic strain ( Trichophyton rubrum —ATCC 28188), according to previous works [ 51 , 52 ]. The fungal inoculum suspension of each strain was added to nanoformulation to obtain a concentration of approximately 1–5 × 10 5 and 1–5 × 10 3 CFU/mL for yeast and for dermatophyte, respectively.…”

“…A fungistatic or fungicidal action was defined when a decrease <99.9% log 10 CFU/mL or ≥99.9% log 10 CFU/mL was observed, respectively. This effect is compared to the starting inoculum at time zero [ 51 , 52 ].…”