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Preclinical Studies with 5,10,15‐Tris(4‐Methylpyridinium)‐20‐Phenyl‐[21 H ,23 H ]‐Porphine Trichloride for the Photodynamic Treatment of Superficial Mycoses Caused by Trichophyton rubrum
Author(s) -
Smijs Threes G. M.,
Pavel Stan,
Talebi Mojgan,
Bouwstra Joke A.
Publication year - 2009
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.2008.00468.x
Subject(s) - trichophyton rubrum , penetration (warfare) , photodynamic therapy , chemistry , dermatophyte , in vivo , trichophyton , stratum corneum , ex vivo , nuclear chemistry , citric acid , microbiology and biotechnology , in vitro , biology , biochemistry , antifungal , organic chemistry , engineering , genetics , operations research
Dermatophytes are fungi that cause infections of keratinized tissues. We have recently demonstrated the susceptibility of the dermatophyte Trichophyton rubrum to photodynamic treatment (PDT) with 5,10,15‐Tris(4‐methylpyridinium)‐20‐phenyl‐[21 H ,23 H ]‐porphine trichloride (Sylsens B) in 5 m m citric acid/sodium citrate buffer (pH 5.2, formulation I). In this work, we examined the penetration of Sylsens B in healthy and with T. rubrum infected skin and we investigated the susceptibility of T. rubrum to PDT using formulation I and UVA‐1 radiation (340–550 nm). Skin penetration studies were performed with formulations I and II (Sylsens B in PBS, pH 7.4) applied on dermatomed skin, human stratum corneum (SC), disrupted SC by T. rubrum growth and SC pretreated with a detergent. No penetration was observed in healthy skin. Disruption of SC by preceding fungal growth caused Sylsens B penetration at pH 7.4, but not at pH 5.2. However, chemically damaged SC allowed Sylsens B to penetrate also at pH 5.2. UVA‐1 PDT was applied ex vivo during two fungal growth stages of two T. rubrum strains (CBS 304.60 and a clinical isolate). Both strains could be killed by UVA‐1 alone (40 J/cm 2 ). Combined with formulation I (1 and 10 μ m Sylsens B for, respectively, CBS 304.60 and the clinical isolate), only 18 J/cm 2 UVA‐1 was required for fungal kill. Therefore, PDT with 10 μ m Sylsens B (formulation I) and 18 J/cm 2 UVA‐1 could be considered as effective and safe. This offers the possibility to perform clinical studies in future.