Topical nitric oxide releasing nanoparticles are effective in a murine model of dermal Trichophyton rubrum dermatophytosis

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Mordorski, Breanne
Costa-Orlandi, Caroline Barcelos [UNESP]
Baltazar, Ludmila M.
Carreño, Leandro J.
Landriscina, Angelo
Rosen, Jamie
Navati, Mahantesh
Mendes-Giannini, Maria Jose Soares [UNESP]
Friedman, Joel M.
Nosanchuk, Joshua D.
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Systemic therapies are preferred for treating dermal dermatophytosis due to inadequate penetration of topical agents. However, systemic antifungals are associated with off-target effects and limited tissue penetration, and antimicrobial resistance is a growing concern. To address this, we investigated topical nitric oxide-releasing nanoparticles (NO-np), which have been used against superficial fungal infections and bacterial abscesses. In addition to enhanced penetration and permeation conferred by nanoparticles, nitric oxide, a broad-spectrum multi-mechanistic antimicrobial agent, offers decreased likelihood of resistance development. In the current study, NO-np inhibited Trichophyton rubrum in vitro, as well as in a murine model of dermal dermatophytosis. In mice, NO-np reduced fungal burden after three days, with complete clearance after seven. Furthermore, NO-np decreased tissue IL-2, 6, 10 and TNFα, indicating earlier attenuation of the host inflammatory response and decreased tissue morbidity. Thus, topical NO-np represent an attractive alternative to systemic therapy against dermal T. rubrum infection.
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Nanomedicine: Nanotechnology, Biology, and Medicine, v. 13, n. 7, p. 2267-2270, 2017.