Potential of Naftifine Application for Transungual Delivery.

Vitalis Briedis,Indrė Šveikauskaitė

doi:10.3390/molecules25133043

Vitalis Briedis, Indrė Šveikauskaitė

Open Access

https://doi.org/10.3390/molecules25133043

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Abstract

Naftifine is used to treat fungal skin infections as it inhibits dermatophytes, which are the cause of onychomycosis. However, naftifine’s ability to permeate the human nail barrier has not been investigated, thus, the antimycotic potential is not clearly established. This work aims to evaluate the effect of penetration enhancing factors on the accumulation of naftifine hydrochloride through human nail clippings. Naftifine polymeric nail lacquers with Eudragit RL100 were developed as a suitable delivery system. Low penetration of naftifine into nail has been determined as less than 10% of applied drug dose accumulated in the nail layers. Incorporation of thioglycolic acid into formulations resulted in increased accumulation of antifungal agent in the nail layers by 100% compared with a control group. Salicylic acid did not effect naftifine accumulation in the human nail. The permeation of naftifine through the nail increased by threefold when the thioglycolic acid-containing formulation was applied and the nail was pretreated with a fractional CO2 laser. Structural changes of the nail barrier, induced by fractional CO2 laser, were visualized by microscopy. The results suggest, that naftifine nail penetration could be significantly increased when physical and chemical enhancing factors are applied.

Highlights

The structure and specificity of biological barriers affect the penetration and bioavailability of drug substances
The selection of chemical enhancers was performed by evaluating the accumulation of naftifine hydrochloride in bovine hooves membranes that were used as a nail model
Monti et al [31] validated bovine hoof membranes as a model for infected human toenails, and this nail model is widely used in penetration studies, especially in the case of the limited availability of human nail plates [32,33]

Summary

Introduction

The structure and specificity of biological barriers affect the penetration and bioavailability of drug substances. Changes of barrier properties in pathology become an additional challenge in permeation studies, as the human nail is one of the natural barriers that changes during infections, and creates additional limitations for efficient therapy. Local treatment of onychomycosis lasts over a year, with the efficacy of up to 50%, but interactions with other medicinal products are avoided, and treatment can be given to all patient groups [3]. Local infection treatment is complicated by the structure of the nail, made up of 80% keratin. Keratin molecules are linked by disulfide bonds, resulting in one of the strongest barriers in the human body, which demonstrates limited permeability for lipophilic antifungal agents [4]. A human nail is composed of the nail plate (thin structure of approximately 25 layers of keratinocytes with keratin filaments matrix)

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