Efficacy of antifungal <scp>PACT</scp> in an <i>in vitro</i> model of onychomycosis

Mehra, Tarun; Schaller, Martin; Walker, Britta; Braunsdorf, Christina; Mailänder-Sánchez, Daniela; Schynowski, F; Hahn, Rosane Christine; Röcken, Martin; Köberle, Martin; Borelli, Claudia

doi:10.1111/jdv.12467

Cited by 11 publications

(11 citation statements)

References 15 publications

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“…The promising results encouraged researchers to apply the 3 formulation in a patient with confirmed onychomycosis. The use of three PACT sessions over the week led to a significant improvement in nail morphology, confirmed in a 6-month follow-up [62]. The effectiveness of PACT and cyclopiroxolamine against T. rubrum dermatophytes was also experimentally compared.…”

Section: Toluidine Blue O and New Toluidine Blue Omentioning

confidence: 80%

“…After 60 s of incubation followed by 30 s irradiation, it turned out that this procedure was effective against each strain, and an increase in activity was observed with an increasing light dose (dose equal 24 J/cm 2 at the light-source power 400 mW) [61]. After initial in vitro tests against Trichopyton rubrum, 3 also found an application in the treatment of onychomycosis [62]. The use of PS in the in vitro model at a concentration of 20 µg/mL after 30 min irradiation with 200 J/cm 2 light led to complete eradication of fungi.…”

Section: Toluidine Blue O and New Toluidine Blue Omentioning

confidence: 96%

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Photosensitizers Mediated Photodynamic Inactivation against Fungi

Ziental

Mlynarczyk

Czarczyńska-Goślińska

et al. 2021

Nanomaterials

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Superficial and systemic fungal infections are essential problems for the modern health care system. One of the challenges is the growing resistance of fungi to classic antifungals and the constantly increasing cost of therapy. These factors force the scientific world to intensify the search for alternative and more effective methods of treatment. This paper presents an overview of new fungal inactivation methods using Photodynamic Antimicrobial Chemotherapy (PACT). The results of research on compounds from the groups of phenothiazines, xanthanes, porphyrins, chlorins, porphyrazines, and phthalocyanines are presented. An intensive search for a photosensitizer with excellent properties is currently underway. The formulation based on the existing ones is also developed by combining them with nanoparticles and common antifungal therapy. Numerous studies indicate that fungi do not form any specific defense mechanism against PACT, which deems it a promising therapeutic alternative.

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Section: Toluidine Blue O and New Toluidine Blue Omentioning

confidence: 80%

Section: Toluidine Blue O and New Toluidine Blue Omentioning

confidence: 96%

Photosensitizers Mediated Photodynamic Inactivation against Fungi

Ziental

Mlynarczyk

Czarczyńska-Goślińska

et al. 2021

Nanomaterials

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“…Mehra et al . ( 2015 ) demonstrated that TBO‐mediated aPDT effectively inhibited the growth of T. rubrum in onychomycosis ex vivo model. In line with these previous studies, the present study used healthy human nail pieces and microconidia of T. rubrum to establish tinea unguium ex vivo model and investigated the photodynamic treatment effect of AE for onychomycosis.…”

Section: Discussionmentioning

confidence: 99%

Aloe‐emodin‐mediated antimicrobial photodynamic therapy against dermatophytosis caused by Trichophyton rubrum

Zhang

Cui

et al. 2021

Microbial Biotechnology

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Trichophyton rubrum is responsible for the majority of dermatophytosis. Current systemic and topical antifungals against dermatophytosis are often tedious and sometimes unsatisfactory. Antimicrobial photodynamic therapy (aPDT) is a non-invasive alternative suitable for the treatment of superficial fungal infections. This work investigated the photodynamic inactivation efficacy and effects of aloe-emodin (AE), a natural photosensitizer (PS) against T. rubrum microconidia in vitro, and evaluated the treatment effects of AE-mediated aPDT for T. rubrum-caused tinea corporis in vivo and tinea unguium ex vivo.The photodynamic antimicrobial efficacy of AE on T. rubrum microconidia was evaluated by MTT assay. The inhibition effect of AE-mediated aPDT on growth of T. rubrum was studied. Intracellular location of AE, damage induced by AE-mediated aPDT on cellular structure and surface of microconidia and generation of intracellular ROS were investigated by microscopy and flow cytometry. The therapeutic effects of AE-mediated aPDT against dermatophytosis were assessed in T. rubrum-caused tinea corporis guinea pig model and tinea unguium ex vivo model. AE-mediated aPDT effectively inactivated T. rubrum microconidia in a light energy dosedependent manner and exhibited strong inhibitory effect on growth of T. rubrum. Microscope images indicated that AE is mainly targeted to the organelles and caused damage to the cytoplasm of microconidia after irradiation through generation of abundant intracellular ROS. AE-mediated aPDT demonstrated effective therapeutic effects for T. rubrum-caused tinea corporis on guinea pig model and tinea unguium in ex vivo model. The results obtained suggest that AE is a potential PS for the photodynamic treatment of dermatophytosis caused by T. rubrum, but its permeability in skin and nails needs to be improved.

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“…This study reports on one of our MFPSs designed for PDT of dermatophytic onychomycoses. With respect to the effectiveness of different onychomycosis treatment strategies, various models have been developed recently [ 19 , 20 , 21 ]. Although many of these models use a realistic topical drug application, they have done so on bovine hoof as a keratin source instead of human nail material [ 20 , 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…The nail penetration behavior, however, will also be affected by the presence of fungal growth. On the other hand, the model used by Mehra et al [ 19 ] included T. rubrum- infected human keratin but obtained this material from powdered nails. This implies that one of the onychomycosis treatment obstacles, the stiffness of the nail plate, cannot be tested in this model.…”

Section: Discussionmentioning

confidence: 99%

Effective Single Photodynamic Treatment of ex Vivo Onychomycosis Using a Multifunctional Porphyrin Photosensitizer and Green Light

Hollander

Visser

Haas

et al. 2015

JoF

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Onychomycosis is predominantly caused by the dermatophytes Trichophyton rubrum, Trichophyton mentagrophytes and Trichophyton tonsurans. The main treatment obstacle concerns low nail-plate drug permeability. In vitro antifungal photodynamic treatment (PDT) and nail penetration enhancing effectiveness have been proven for multifunctional photosensitizer 5,10,15-tris(4-N-methylpyridinium)-20-(4-(butyramido-methylcysteinyl)-hydroxyphenyl)-[21H,23H]-porphine trichloride (PORTHE). This study investigates single PORTHE green laser/LED PDT of varying degrees of ex vivo onychomycoses in a human nail model. T. mentagrophytes, T. rubrum, T. tonsurans onychomycoses were ex vivo induced on nail pieces at 28 °C (normal air) and 37 °C (6.4% CO2) during 3 to 35 days and PDTs applied to the 37 °C infections. All dermatophytes showed increasingly nail plate invasion at 37 °C between 7 and 35 days; arthroconidia were observed after 35 days for T. mentagrophytes and T. tonsurans. Using 81 J/cm2 (532 nm) 7-day T. mentagrophytes onychomycoses were cured (92%) with 80 µM PORTHE (pH 8) after 24 h propylene glycol (PG, 40%) pre-treatment and 35-day onychomycoses (52%–67%) with 24 h PORTHE (40–80 µM)/40% PG treatment (pH 5). 28 J/cm2 LED light (525 ± 37 nm) improved cure rates to 72%, 83% and 73% for, respectively, T. mentagrophytus, T. rubrum and T. tonsurans 35-day onychomycoses and to 100% after double PDT. Data indicate PDT relevance for onychomycosis.

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Efficacy of antifungal PACT in an in vitro model of onychomycosis

Abstract: PACT appears to be an effective treatment of onychomycosis in vitro. The promising results need to be validated by clinical trials.

Cited by 11 publications

References 15 publications

Photosensitizers Mediated Photodynamic Inactivation against Fungi

Photosensitizers Mediated Photodynamic Inactivation against Fungi

Aloe‐emodin‐mediated antimicrobial photodynamic therapy against dermatophytosis caused by Trichophyton rubrum

Effective Single Photodynamic Treatment of ex Vivo Onychomycosis Using a Multifunctional Porphyrin Photosensitizer and Green Light

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