Onychomycosis is a very common illness that befalls an increasing number of individuals worldwide and involves a fungal infection of the nails. Currently, orally or topically administrated antimycotics are in use for the treatment of onychomycosis. However, these current treatments are unsatisfactory regarding efficiency, safety and costs. This justifies the efforts to look for alternative treatment modalities. This dissertation investigates the impact of photodynamic inactivation (PDI) against dermatophytes and molds. Three of the causing pathogens of the dermatological disease onychomycosis are under investigation: Trichophyton rubrum (T. rubrum), Trichophyton interdigitale (T. interdigitale) and the mold Scopulariopsis brevicaulis (S. brevicaulis).
To assess the potential of PDI against onychomycosis causing pathogens, phototoxicity tests were performed using three photosensitizers (PSs): the cationic 5,10,15,20-Tetrakis(1- methylpyridinium-4-yl) porphyrintetra(p-toluenesulfonate) (TMPyP) and 5,10,15-tris-(1- methylpyridinium-2-yl) corrolato-(trans-dihydroxo) phosphorus(V) (PCor+) as well as the anionic 4',5',7'-tetrabromo-3',6'-dihydroxyspiro[2-benzofuran-3,9'-xanthene]-1-one (Eosin Y). Alongside the phototoxicity tests, time resolved singlet oxygen luminescence scans were conducted to serve as a control method of PDI. The research strategy was to start with in vitro experiments on spore suspensions and on surfaces followed by ex vivo tests on infected human nails. For each of these stages, the results of phototoxicity were correlated with the singlet oxygen scans. All three PSs proved to have a high phototoxic effect against the three fungi species in vitro. Those could be correlated with singlet oxygen measurements, where a high singlet oxygen luminescence signal was acquired. Contrary to the expectations from the in vitro experiments were the results obtained ex vivo: On infected human nails, the PSs were not able to induce a phototoxic effect. Singlet oxygen scans conducted to get insight into the reasons behind these results showed nearly no singlet oxygen luminescence signal on human nails. Enrichment of the atmosphere with oxygen lead to a slight improvement of the signal. Addressing the various known challenges associated with PDI on infected human nails - like the nail plate rigidity and its chemical composition - by enhancing the permeability of the nail plate and additional oxygenation, PDI would have a great impact within short time on treating the toenail fungal infection. This study, for the first time, shows the correlation between PDI treatment of onychomycosis and singlet oxygen.
|Advisor:||Röder , Beate , Benson , Oliver , Karmer , Axel|
|School:||Humboldt Universitaet zu Berlin (Germany)|
|Source:||DAI-C 81/8(E), Dissertation Abstracts International|
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