Abstract
Candida albicans is a leading fungal cause of burn infections in hospital settings, and sepsis is one of the principle causes of death after a severe burn. The prevalence of invasive candidiasis in burn cases varies widely, but it accounts for 3–23% of severe infection with a mortality rate ranging from 14 to 70%. Therefore, it is imperative that we develop innovative therapeutics to which this fungus is unlikely to evolve resistance, thus curtailing the associated morbidity and mortality and ultimately improving our capacity to treat these infections. An inexpensive and stable nitric oxide (NO)-releasing nanoparticle (NO-np) platform has been recently developed. NO is known to have direct antifungal activity, modulate host immune responses and significantly regulate wound healing. In this study, we hypothesized that NO-np would be an effective therapy in the treatment of C. albicans burn infections. Using a murine burn model, NO-np demonstrated antifungal activity against C. albicans in vivo, most likely by arresting its growth and morphogenesis as demonstrated in vitro. NO-np demonstrated effective antimicrobial activity against yeast and filamentous forms of the fungus. Moreover, we showed that NO-np significantly accelerated the rate of wound healing in cutaneous burn infections when compared to controls. The histological evaluation of the affected tissue revealed that NO-np treatment modified leukocyte infiltration, minimized the fungal burden, and reduced collagen degradation, thus providing potential mechanisms for the therapeutics’ biological activity. Together, these data suggest that NO-np have the potential to serve as a novel topical antifungal which can be used for the treatment of cutaneous burn infections and wounds.
Highlights
Sepsis is one of the leading causes of death after a severe burn injury
We recently developed and characterized an inexpensive and stable nitric oxide (NO)-releasing nanoparticle (NO-np) platform using nanotechnology based on a silane hydrogel (Eggimann et al, 2003b)
Candida albicans has emerged as a major agent of hospitalacquired infections and this fungus has a high incidence of progression from focal infection to invasive and/or systemic diseases in specific patient subpopulations such as burn victims (Holzheimer and Dralle, 2002)
Summary
Sepsis is one of the leading causes of death after a severe burn injury. The rate of microbial infection is estimated to range from 30 to 63% among all burn victims admitted to burn centers, with the incidence associated with the severity of injury and the duration of hospital stay (Holzheimer and Dralle, 2002). We recently developed and characterized an inexpensive and stable nitric oxide (NO)-releasing nanoparticle (NO-np) platform using nanotechnology based on a silane hydrogel (Eggimann et al, 2003b) This technology has the potential to serve as a novel, applied, topical delivery system for antimicrobials, such as NO, which can be used for the treatment of complex cutaneous infections and wounds. In both physiologic and pathologic conditions, NO maintains skin homeostasis by regulating circulation, ultraviolet-mediated melanogenesis, and sunburn erythema, which all participate in the maintenance of the skin as a protective barrier against microorganisms (Frank et al, 2002). Based on our previous work and the fact that NO transits most if not all biological barriers, we have www.frontiersin.org
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