Nanoparticle Encapsulation of Amphotericin B: Effective Topical Antifungal in the Setting of a Burn Wound

Candida albicans and emerging non-albicans species are clinically relevant fungal pathogens in the context of extensive burn wounds as severe-burn victims are susceptible to invasive candidasis, a fungal sepsis with a ~14-70% crude mortality rate.  Due to increased antifungal resistance amongst Candida spp., the use of potent fungicidal therapeutics evincing minimal resistance such as amphotericin B (Amp) are warranted.  Unfortunately, current administrations of Amp are only available orally or parentally; these are suboptimal as nephrotoxicity and infusion-related adversities often result.  In order to circumvent these unintended sequelae, we investigated nanoparticle encapsulation of Amp as a topical therapeutic against invasive candidiasis.  Capitalizing on a technique previously utilized to encapsulate nitric oxide, Amp was sequestered into a silane-based hydrogel nanoparticle system.  We hypothesized that Amp nanoparticles (Amp-np) and solubilized Amp (Amp-sol) would demonstrate commensurate fungicidal capability in vitro against Candida spp. clinical isolates.  Release kinetics provided evidence of steady Amp release at 1.7μg/mL for 24 hrs.  Via MICs and metabolic growth curves, it was determined that all strains of Candida spp. demonstrated equal or enhanced susceptibility when subjected to Amp-np treatment in comparison to Amp-sol.  XTT viability assays also showcased equilibrated inhibition of biofilm formation by Amp-np.  Lastly, mice with burn lesions were inoculated with 10⁷ Candida albicans cells to test the efficacy of Amp-np.  Preliminary data suggests Amp-np exhibits superior efficiency in fungal clearance and wound healing relative to Amp-sol.  These data corroborate the notion that Amp-np can function as a topical antifungal in the setting of a burn wound.