Effective Single Photodynamic Treatment of ex Vivo Onychomycosis Using a Multifunctional Porphyrin Photosensitizer and Green Light

Onychomycosis is predominantly caused by the dermatophytes Trichophyton rubrum, Trichophyton mentagrophytes and Trichophyton tonsurans. The main treatment obstacle concerns low nail-plate drug permeability. In vitro antifungal photodynamic treatment (PDT) and nail penetration enhancing effectiveness have been proven for multifunctional photosensitizer 5,10,15-tris(4-N-methylpyridinium)-20-(4-(butyramidomethylcysteinyl)- hydroxyphenyl)-[21H, 23H]-porphine trichloride (PORTHE). This study investigates single PORTHE green laser/LED PDT of varying degrees of ex vivo onychomycoses in a human nail model. T. mentagrophytes, T. rubrum, T. tonsurans onychomycoses were ex vivo induced on nail pieces at 28 degrees C (normal air) and 37 degrees C (6.4% CO2) during 3 to 35 days and PDTs applied to the 37 degrees C infections. All dermatophytes showed increasingly nail plate invasion at 37 degrees C between 7 and 35 days; arthroconidia were observed after 35 days for T. mentagrophytes and T. tonsurans. Using 81 J/cm(2) (532 nm) 7-day T. mentagrophytes onychomycoses were cured (92%) with 80 mu M PORTHE (pH 8) after 24 h propylene glycol (PG, 40%) pre-treatment and 35-day onychomycoses (52%-67%) with 24 h PORTHE (40-80 mu M)/40% PG treatment (pH 5). 28 J/cm(2) LED light (525 +/- 37 nm) improved cure rates to 72%, 83% and 73% for, respectively, T. mentagrophytus, T. rubrum and T. tonsurans 35-day onychomycoses and to 100% after double PDT. Data indicate PDT relevance for onychomycosis.