Amphotericin B releasing nanoparticle topical treatment of Candida spp. in the setting of a burn wound

Candida spp. infection in the context of burn wounds leads to invasive disease with a 14–70% mortality rate. Unfortunately, current administrations of AmB, an important therapeutic demonstrating minimal resistance, are only available via potentially cytotoxic IV infusions. In order to circumvent these sequelae, we investigated the efficacy of nanoparticle encapsulated AmB (AmB-np) as a topical therapeutic against Candida spp. (drug release equilibrated solubilized AmB [AmB-sol] included as control). Clinical strains demonstrated equal or enhanced killing efficacy with 72.4–91.1% growth reduction by 4 hours. AmB-nps resulted in statistically significant reduction of fungal biofilm metabolic activity ranging from 80% to 95% viability reduction (P< 0.001). Using a murine full-thickness burn model, AmB-np exhibited a quicker efficiency in fungal clearance versus AmB-sol by day three, although wound healing rates were similar. These data support the concept that AmB-np can function as a topical antifungal in the setting of a burn wound.From the Clinical EditorThe control of fungal infections with Candida species remains a challenge in the context of burn wounds. A nanoencapsulated topical amphotericin-B compound was studied in a murine model of full thickness burn injury, showing remarkable efficacy in controlling Candida infection. This may become a viable alternative to the potentially toxic intravenous formulations.

Graphical AbstractAmphotericin B was sequestered into a silane-hydrogel nanoparticle vehicle to test its potential as a topical agent against Candida spp. Nanoparticle encapsulation of AmB-np can mitigate systemic side effects and provide localized targeting. Amphotericin B nanoparticles (AmB-np) demonstrated efficacy in vitro against clinical strains (biofilm and yeast) and also effectively reduced fungal burden in vivo using a murine full-thickness burn wound model. Collectively, this data suggests that AmB-np may have clinical utility against Candida spp. burn wound infection.Figure optionsDownload high-quality image (191 K)Download as PowerPoint slide