Effective photosensitization and selectivity in vivo of Candida Albicans by meso-tetra (N-methyl-4-pyridyl) porphine tetra tosylate.

Background and Objective: The fungus Candida albicans commonly causes mucosal and cutaneous infections in patients with impaired immunity. We investigated the effectiveness of the photosensitizer meso-tetra (N-methyl-4-pyridyl) porphine tetra tosylate (TMP-1363) in the photodynamic treatment (PDT) of C. albicans infection in vitro and its selectivity in an animal model.
Materials and Methods: The efficacy of TMP-1363 in PDT of C. albicans in vitro was compared to that of methylene blue (MB) using a colony forming unit (CFU) assay. In vivo infection in the mouse was established by inoculation of C. albicans yeast in the intradermal space of the ear pinna. Two days post-infection, 0.3 mg ml(-1) TMP-1363 was administered topically. Thirty minutes after TMP-1363 application, the ears were irradiated at 514 nm using a fluence of 90 J cm(-2) delivered at an irradiance of 50 mW cm(-2) . The ears were excised 2 hours post-irradiation, homogenized, and the organism burden was determined by a CFU assay. In vivo wide field and confocal fluorescence imaging assessed the localization of the photosensitizer in relationship to C. albicans.
Results: Photosensitization with TMP-1363 resulted in a greater than three-log increase in killing of C. albicans in vitro compared to MB. In vivo fluorescence imaging demonstrated a high degree of selective labeling of C. albicans by TMP-1363. PDT of infection using TMP-1363 resulted in a significant reduction in CFU/ear relative to untreated controls. Infected ears subjected to PDT displayed complete healing over time with no observable damage to the pinna.
Conclusion: Our in vitro and in vivo findings support TMP-1363-mediated PDT as a viable therapeutic approach for the PDT of candidiasis.
(Copyright © 2011 Wiley-Liss, Inc.)