title: Amphotericin B releasing nanoparticle topical treatment of Candida spp. in the setting of a burn wound.
abstract: 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.
  
  
  BACKGROUND
  The 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.
authors.affiliation: Department of Medicine (Division of Infectious Diseases), Albert Einstein College of Medicine, Bronx, New York.
authors.forename: David A
authors.initials: DA
authors.lastname: Sanchez
authors.affiliation: Department of Medicine (Division of Dermatology), Albert Einstein College of Medicine, Bronx, New York.
authors.forename: David
authors.initials: D
authors.lastname: Schairer
authors.affiliation: Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Chaim
authors.initials: C
authors.lastname: Tuckman-Vernon
authors.affiliation: Department of Medicine (Division of Dermatology), Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Jason
authors.initials: J
authors.lastname: Chouake
authors.affiliation: Department of Medicine (Division of Dermatology), Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Allison
authors.initials: A
authors.lastname: Kutner
authors.affiliation: Department of Medicine (Division of Dermatology), Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Joy
authors.initials: J
authors.lastname: Makdisi
authors.affiliation: Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Joel M
authors.initials: JM
authors.lastname: Friedman
authors.affiliation: Department of Medicine (Division of Infectious Diseases), Albert Einstein College of Medicine, Bronx, New York; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Nosanchuk
authors.affiliation: Department of Medicine (Division of Dermatology), Albert Einstein College of Medicine, Bronx, New York; Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, New York. Electronic address: adfriedm@montefiore.org.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Friedman
mesh_terms: D000287:Administration, Topical; D000666:Amphotericin B / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D002056:Burns / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D002175:Candida / Q000187:drug effects / Q000472:pathogenicity; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D014947:Wounds and Injuries / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology
chemical_list: D000935:Antifungal Agents; D000666:Amphotericin B
keywords: Amphotericin B; Burn wounds; Candida spp.; Nanoparticles; Topical antifungal