Photodynamic Treatment of the Dermatophyte Trichophyton rubrum and its Microconidia with Porphyrin Photosensitizers^¶

Abstract

The application of photosensitizers for the treatment of fungal infections is a new and promising development within the field of photodynamic treatment (PDT). Dermatophytes, fungi that can cause infections of the skin, hair and nails, are able to feed on keratin. Superficial mycoses are probably the most prevalent of infectious diseases in all parts of the world. One of the most important restrictions of the current therapeutic options is the return of the infection and the duration of the treatment. This is especially true in the case of infections of the nail (tinea unguium) caused by Trichophyton rubrum, an anthropophilic dermatophyte with a worldwide distribution. Recently, we demonstrated that 5,10,15‐tris(4‐methylpyridinium)‐20‐phenyl‐[21H,23H]‐porphine trichloride (Sylsens B) and deuteroporphyrin monomethylester were excellent photosensitizers toward T. rubrum when using broadband white light. This study demonstrates the photodynamic activity of these photosensitizers with red light toward both a suspension culture of T. rubrum and its isolated microconidia. The higher penetration depth of red light is important for the PDT of nail infections. In addition, we tested the photodynamic activity of a newly synthesized porphyrin, quinolino‐[4,5,6,7‐efg]‐7‐demethyl‐8‐deethylmesoporphyrin dimethylester, displaying a distinct peak in the red part of the spectrum. However, its photodynamic activity with red light toward a suspension culture of T. rubrum appeared to be only fungistatic. Sylsens B was the best photosensitizer toward both T. rubrum and its microconidia. A complete inactivation of the fungal spores and destruction of the fungal hyphae was found. In studies into the photostability, Sylsens B appeared to be photostable under the conditions used for fungal PDT. A promising result of this study is the demonstration of the complete degradation of the fungal hyphae in the time after the PDT and the inactivation of fungal spores, both with red light. These results offer the ingredients for a future treatment of fungal infections, including those of the nail.

Photodynamic Therapy for Distal and Lateral Subungual Toenail Onychomycosis Caused by Trichophyton rubrum: Preliminary Results of a Single-centre Open Trial

“…In vitro studies have demonstrated that T. ruhrum is able to metabolize 5-aminolevulinic acid (ALA) to protoporphyrin IX, and that PDT leads to significant reduction in its growth (2)(3)(4)(5).…”

Topical Antimicrobials for Burn Wound Infections

“…A further patent [194] described the use of these porphyrins typified by Sylsens B (Fig 10) for carrying out PDT of fungal skin infections including burns.…”

Caracterização do perfil de susceptibilidade de isolados clínicos de <i>Neoscytalidium dimidiatum</i> e <i>N. dimidiatum</i> var. <i>hyalinum</i> aos antifúngicos e a fotossensibilizadores

“…Os fotossensibilizadores são compostos atóxicos ou pouco tóxicos, inativos em seu estado fundamental, que absorvem luz na região do visível (Jori, 2006). Quando o fotossensibilizador é exposto à radiação com comprimentos de onda apropriados, sua molécula é excitada, levando a uma série de transferências moleculares de energia que Introdução_________________________________________________________________________ normalmente originam espécies reativas de oxigênio (EROs), como o oxigênio singlete 1 O 2, o ânion superóxido e o radical hidroxila, que são extremamente reativos e citotóxicos (Soukos et al, 1998;Friedberg et al, 2001;Hambling et al, 2002;Smijs et al, 2004). Os fotossensibilizadores baseados na fenotiazina (phenothiazinum based photosensitisers -PhBPs), como o azul de metileno, possuem estrutura heteroaromática planas que conferem às suas moléculas propriedades fotossensibilizadoras.…”