Investigation of conditions involved in the susceptibility of the dermatophyte Trichophyton rubrum to photodynamic treatment.
BACKGROUND
Photodynamic treatment (PDT) refers to a treatment with light-activated agents (photosensitizers) in combination with visible light and molecular oxygen. Recently, we have demonstrated that the porphyrins, 5,10,15-tris(4-methylpyridinium)-20-phenyl-[21H,23H]-porphine trichloride (Sylsens B) and deuteroporphyrin monomethylester (DP mme) are excellent photosensitizers to be used against Trichophyton rubrum both in vitro and ex vivo.


OBJECTIVE
The objective of this study was to investigate the key factors involved in PDT efficacy of both photosensitizers in an ex vivo situation during different fungal growth stages using a recently developed ex vivo model. The study focused on the influence of pH and ion strength of incubation media, photochemical properties of the photosensitizers (spectra and singlet oxygen production), and the effect of several scavengers of reactive oxygen species (sodium azide, histidine, mannitol) and phenylmethylsulphonylfluoride (keratinase inhibitor) on the PDT efficacy.


CONCLUSIONS
The results show that an optimal pH and low concentrations of calcium are crucial for a selective binding of Sylsens B to the fungus, leading to an increased PDT efficacy. This selective binding to T. rubrum cannot be accomplished for DP mme. It can be concluded that the prerequisite for successful treatment is a use of a low molarity solution of pH 5, supplemented with a chelating agent and a keratinase activity-repressing agent. Under these conditions, PDT with Sylsens B inactivates, initially via singlet oxygen, effectively the fungus in different fungal growth stages.
Smijs
Threes G M
TG
Leiden University Medical Centre, Leiden, The Netherlands. G.M.T.Smijs@LUMC.nl
Bouwstra
Joke A
JA
Talebi
Mojgan
M
Pavel
Stan
S
D000935:Antifungal Agents / Q000494:pharmacology*; D003905:Deuteroporphyrins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D016166:Free Radical Scavengers; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D050296:Microbial Viability; D015394:Molecular Structure; D009994:Osmolar Concentration; D010778:Photochemotherapy; D011166:Porphyrins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013057:Spectrum Analysis; D014249:Trichophyton / Q000187:drug effects*
C509254:5,10,15-tris(4-methylpyridinium)-20-phenyl-(21H,23H)-porphine; D000935:Antifungal Agents; D003905:Deuteroporphyrins; D016166:Free Radical Scavengers; D011166:Porphyrins; D011726:Pyridinium Compounds; C509255:deuteroporphyrin monomethylester