Simultaneous Topical Antifungal Skin and Nail Therapy: A Prospective Treatment Option?

Abstract

Superficial fungal infections affect 20 – 25 % of the world’s population with an increasing trend. Common infections are fungal skin and nail diseases (tinea pedis and onychomycosis, respectively), which often occur simultaneously due to autoinoculation. Tinea pedis is mostly provoked by the dermatophyte fungus Trichophyton rubrum, which remains in the outermost skin layer, the stratum corneum (SC). Normally, the treatment is done topically and takes up to four weeks. Just as tinea pedis, about 90 % of onychomycoses is triggered by T. rubrum and Trichophyton mentagrophytes. Toenail onychomycosis is 4 – 10 times more common in comparison to fingernails. The nail plate is 0.25 – 1.0 mm thick and consists of densely packed keratin cell layers. With a water content of up to 25 % and a lipid content of 0.1 – 1 %, the nail plate is considered as a hydrophilic gel membrane with an additional lipophilic route. Due to its excellent barrier properties and a growth rate of only 2 – 3 mm per month, nail mycosis treatment is a remarkable challenge and is often accompanied by high relapse rates. In contrast to the nail plate, SC is considered as an approximately 10 µm thick, predominantly lipophilic barrier. Because of the distinct structure of these tissues, hitherto, there are only formulations marketed for either tinea pedis or onychomycosis. A formulation targeting both would therefore be a considerable improvement, but has to fulfil different characteristics.

The following review focuses on potential active pharmaceutical ingredients (API) for simultaneous tinea pedis and onychomycosis treatment as well as in vitro models for antifungal efficacy evaluation. It carves out the challenges in simultaneous therapy based on the distinct structure of nail and SC.

Zusammenfassung

Oberflächliche Pilzinfektionen betreffen 20 – 25 % der Weltbevölkerung mit steigender Tendenz. Häufige Infektionen sind Haut- und Nagelpilzerkrankungen (Tinea pedis bzw. Onychomykose), die wegen Autoinokulation oft gleichzeitig auftreten. Tinea pedis wird meist durch den Dermatophyten Trichophyton rubrum ausgelöst, der in der obersten Hautschicht verbleibt, dem Stratum corneum (SC). Üblich ist eine bis zu vier Wochen dauernde topische Behandlung. Genauso wie Tinea pedis werden etwa 90 % der Onychomykosen durch T. rubrum und Trichophyton mentagrophytes ausgelöst. Onychomykose der Zehennägel ist dabei 4 – 10-mal häufiger als die der Fingernägel. Die Nagelplatte ist 0,25 – 1,0 mm dick und besteht aus dicht gepackten Keratin-Zellschichten. Mit einem Wassergehalt von bis zu 25 % und einem Lipidgehalt von 0,1 bis 1 % wird sie als hydrophile Gelmembran mit einer zusätzlichen lipophilen Route angesehen. Wegen ihrer hervorragenden Barriereeigenschaften und einer Wachstumsrate von nur 2 – 3 mm pro Monat stellt die Behandlung von Nagelpilz eine besondere Herausforderung dar und wird oft von Rückfällen begleitet. Im Unterschied zur Nagelplatte wird das SC als etwa 10 µm dicke, überwiegend lipophile Barriere betrachtet. Wegen der unterschiedlichen Struktur der Gewebe werden bisher Formulierungen entweder gegen Tinea pedis oder Onychomykose vermarktet. Eine Formulierung, die beides bekämpft, wäre daher eine beträchtliche Verbesserung. Allerdings muss diese verschiedene Eigenschaften erfüllen.

Der obige Beitrag konzentriert sich auf potenzielle pharmazeutische Wirkstoffe für die simultane Tinea pedis- und Onychomykose-Behandlung sowie In-vitro-Modelle für die Bewertung der antimykotischen Wirksamkeit. Es werden die Herausforderungen einer Simultantherapie auf der Grundlage der unterschiedlichen Strukturen des Nagels und des SC herausgearbeitet.

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