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Ex vivo nail infection as an effective preclinical method for screening of new topical antifungals
P M Quatrin1, T F A Kaminski2, S J Berlitz3
1Programa de Pós-Graduação em Microbiologia Agrícola e do Ambiente, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Abstract:
Onychomycosis are fungal nail infections comprising of about 50% of onychopathies and are commonly caused by dermatophytes. The treatment of this dermatomycosis requires a long period of time and is associated with high rates of recurrence. In view of the need to evaluate the antifungal performance of promising preclinical compounds, we developed, in this study, a practical and accessibleex vivo model for establishing a Trichophyton rubrum onychomycosis framework using porcine hooves. This model has as its main advantage the similar structural and three-dimensional characteristics that the porcine hooves have with the human nail. The proposed model allowed to evaluate the antifungal activity of a new antifungal compound and a reference drug (terbinafine), both already incorporated into a nail lacquer for topical use. Treatments with compound 3-selenocyanate-indole (Se4a) and with terbinafine incorporated into this nail lacquer completely inhibited fungal growth, corresponding to the profile of in vitro activity observed against T. rubrum. This study concludes that the ex vivo porcine hoof model is an effective alternative method for preclinical screening of drugs or new topical compounds developed to combat onychomycosis. Further studies are needed to compare the permeability of porcine hooves with human nails permeability.
Insights
A new ex vivo porcine hoof model effectively screens antifungal compounds for onychomycosis (fungal nail infections). This practical model demonstrated that compound Se4a and terbinafine nail lacquers inhibited fungal growth, offering a promising preclinical evaluation method.
Area of Science:
- Mycology
- Dermatology
- Pharmacology
Background:
- Onychomycosis, a common fungal nail infection, presents treatment challenges due to long durations and high recurrence rates.
- Effective preclinical models are crucial for evaluating novel antifungal therapies against dermatophytes.
Purpose of the Study:
- To develop and validate a practical ex vivo model using porcine hooves for onychomycosis research.
- To assess the antifungal efficacy of a novel compound (Se4a) and terbinafine in a topical nail lacquer formulation using this model.
Main Methods:
- Established an ex vivo onychomycosis framework using Trichophyton rubrum on porcine hooves, mimicking human nail structure.
- Applied topical nail lacquers containing compound Se4a and terbinafine to the infected hooves.
- Evaluated the antifungal activity by monitoring fungal growth inhibition.
Main Results:
- The ex vivo porcine hoof model demonstrated structural similarities to human nails, making it suitable for drug screening.
- Both compound Se4a and terbinafine nail lacquers completely inhibited fungal growth of T. rubrum.
- The observed results correlated with in vitro antifungal activity profiles.
Conclusions:
- The ex vivo porcine hoof model is a viable and accessible alternative for preclinical screening of topical antifungal agents for onychomycosis.
- This model facilitates the evaluation of new compounds and drug formulations against fungal nail infections.
- Further research is warranted to compare the permeability characteristics of porcine hooves and human nails.
