title: Preclinical studies with 5,10,15-Tris(4-methylpyridinium)-20-phenyl-[21H,23H]-porphine trichloride for the photodynamic treatment of superficial mycoses caused by Trichophyton rubrum.
abstract: 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-[21H,23H]-porphine trichloride (Sylsens B) in 5 mm 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 microm 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 microm 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.
authors.affiliation: Leiden University Medical Centre, The Netherlands. G.M.T.Smijs@LUMC.nl
authors.forename: Threes G M
authors.initials: TG
authors.lastname: Smijs
authors.forename: Stan
authors.initials: S
authors.lastname: Pavel
authors.forename: Mojgan
authors.initials: M
authors.lastname: Talebi
authors.forename: Joke A
authors.initials: JA
authors.lastname: Bouwstra
mesh_terms: D006801:Humans; D006863:Hydrogen-Ion Concentration; D009181:Mycoses / Q000188:drug therapy* / Q000382:microbiology; D010778:Photochemotherapy; D011166:Porphyrins / Q000627:therapeutic use*; D011726:Pyridinium Compounds / Q000627:therapeutic use*; D014249:Trichophyton / Q000472:pathogenicity*
chemical_list: C509254:5,10,15-tris(4-methylpyridinium)-20-phenyl-(21H,23H)-porphine; D011166:Porphyrins; D011726:Pyridinium Compounds