Infected nail plate model made of human hair keratin for evaluating the efficacy of different topical antifungal formulations against Trichophyton rubrum in vitro

ABSTRACT Onychomycosis is a nail fungal infection, mostly caused by dermatophytes. The treatment efficacy is impaired by difficulties of reaching effective drug levels at the site of infection; frequent relapses occur after cessation of antifungal therapy. The aim of the study was to compare two commercial products containing ciclopirox or efinaconazole for antimycotic activity and antifungal drug resistance. A study of permeation and penetration through bovine hoof membranes, as a nail model, was performed to evaluate the antimycotic activity of permeates against clinical isolates of selected fungi, and the frequency of spontaneous in vitro Trichophyton rubrum-resistant strains was assessed by broth microdilution assays. The results suggest that ciclopirox creates a depot in the nail, leading to a gradual release of the drug over time with action on both the nail plate and bed. Conversely, efinaconazole, mildly interacting with nail keratin, mainly exerts its antifungal activity in the nail bed. However, in the case of T. rubrum, the antifungal activities of the drugs in the nail plate seem comparable. Finally, efinaconazole showed a potential for induction of resistance in T. rubrum, which may limit its efficacy over time. Ciclopirox did not show any potential to induce resistance in T. rubrum and appears endowed with a more complete activity than efinaconazole in the management of onychomycosis as the nail keratin is a substrate for the growth of fungal cells, and the availability of drug in large concentration just in the nail bed may not be sufficient to guarantee the complete eradication of pathogens.

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In vitro evaluation of the antifungal efficacy of poloxamer 407-based formulations in an infected nail plate model

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2016.01.082 ◽

2016 ◽

Vol 505 (1-2) ◽

pp. 20-23 ◽

Cited By ~ 3

Author(s):

Anja Täuber ◽

Christel C. Müller-Goymann

Keyword(s):

Nail Plate ◽

Poloxamer 407 ◽

Plate Model ◽

In Vitro Evaluation ◽

Antifungal Efficacy

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Comparison of the Antifungal Efficacy of Terbinafine Hydrochloride and Ciclopirox Olamine Containing Formulations against the Dermatophyte Trichophyton rubrum in an Infected Nail Plate Model

Molecular Pharmaceutics ◽

10.1021/mp400711q ◽

2014 ◽

Vol 11 (7) ◽

pp. 1991-1996 ◽

Cited By ~ 6

Author(s):

Anja Täuber ◽

Christel C. Müller-Goymann

Keyword(s):

Trichophyton Rubrum ◽

Nail Plate ◽

Plate Model ◽

Ciclopirox Olamine ◽

Terbinafine Hydrochloride ◽

Antifungal Efficacy

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A New In Vitro Model to Evaluate Anti-Adhesive Effect against Fungal Nail Infections

Applied Sciences ◽

10.3390/app11051977 ◽

2021 ◽

Vol 11 (5) ◽

pp. 1977

Author(s):

Paola Perugini ◽

Margherita Bonetti ◽

Marta Guerini ◽

Giorgio Musitelli ◽

Pietro Grisoli

Keyword(s):

Candida Albicans ◽

Social Life ◽

In Vitro Model ◽

Trichophyton Rubrum ◽

Negative Impact ◽

Nail Plate ◽

Negative Control ◽

Pharmaceutical Product ◽

Vitro Model

Nail fungal infection is often mistakenly considered a minor issue or a purely esthetic problem that is not worth solving. However, onychomycosis has been demonstrated to have a negative impact on a patient’s social life. Therefore, given the poor efficacy of various therapy types, there is strong interest in exploring new methods for evaluating antifungal treatments. As such, the aim of this work was to develop a new protocol, using bovine hoof membranes as a model of the human nail to evaluate the capability of a product claiming to prevent fungal adhesion, which is the first step of the infection. In this work, two specific and representative fungal strains, Trichophyton rubrum and Candida albicans, were used. In order to evaluate the possible protective activity of a product against fungal contamination of the nail plate, it was first necessary to test the affinity of the hoof membranes to be contaminated by the fungi. Then, a pharmaceutical product and a base coat were tested as a positive and negative control, respectively, by introducing the membranes (anti-fungal, basic or no treatment and single vs. multiple treatments) into the fungal suspensions for three different contact times (15 min, 5 h and 24 h). The results showed that the more significant antiadhesive effect (AE) was obtained against Trichophyton rubrum than against Candida albicans. Furthermore, taking into account the results obtained at all testing times, 5 h appeared to be the best time for testing the antiadhesive activity. The results obtained after three treatments with drugs and on washed membranes, in comparison to one single application of antifungal product (AP), demonstrated clearly that the drug was able to penetrate deeper into the membranes to exert itself, even after washing and also after only 15 min of contact. Thus, hoof membrane has been shown to be a valuable in vitro model for this kind of product assessment.

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