title: Novel oral amphotericin B formulation (iCo-010) remains highly effective against murine systemic candidiasis following exposure to tropical temperature.
abstract: OBJECTIVE
  To evaluate the antifungal activity of amphotericin B (AmB) in a mouse model of systemic candidiasis following administration of a novel oral AmB formulation (iCo-010) that has been pre-exposed to tropical temperatures.
  
  
  METHODS
  Amphotericin B (AmB) was prepared as a 5 mg/mL dispersion in a mixture of Peceol, Gelucire 44/14 and VitE-TPGS 2,3 (iCo-010). The formulation was protected from light and incubated in a sealed container at 43 °C for 60 days. Mice infected with Candida albicans were treated with either iCo-010 formulation pre-incubated at 43 °C for 60 days or freshly prepared iCo-010 formulation at doses of 5, 10 and 20 mg/kg once daily for five consecutive days. Single intravenous 5 mg/kg dose of AmBisome® was used as a positive control group. Seven days following the last dose, the kidney, liver, spleen, lung, heart and brain were removed and the number of colony forming units (CFUs) was determined as a measure of tissue fungal load. In addition, the concentration of AmB within each tissue was determined using high performance liquid chromatography (HPLC).
  
  
  RESULTS
  There were no significant differences in the reduction of CFUs and the concentration of AmB recovered in all organs at all iCo-010 doses tested between the freshly prepared iCo-010 formulation compared to the formulation that was incubated at 43 °C for 60 days.
  
  
  CONCLUSIONS
  A novel oral AmB formulation, iCo-010, incubated at 43 °C for 60 days to simulate the exposure of the formulation to tropical temperatures remained highly effective against murine systemic candidiasis.
authors.affiliation: a Faculty of Pharmaceutical Sciences , University of British Columbia , Vancouver , BC , Canada .
authors.forename: Kishor M
authors.initials: KM
authors.lastname: Wasan
authors.forename: Olena
authors.initials: O
authors.lastname: Sivak
authors.forename: Karen
authors.initials: K
authors.lastname: Bartlett
authors.forename: Ellen K
authors.initials: EK
authors.lastname: Wasan
authors.forename: Pavel
authors.initials: P
authors.lastname: Gershkovich
mesh_terms: D000284:Administration, Oral; D000666:Amphotericin B / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy*; D002851:Chromatography, High Pressure Liquid; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients / Q000737:chemistry*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D013696:Temperature; D014018:Tissue Distribution; D014329:Tropical Climate
chemical_list: D000935:Antifungal Agents; D005079:Excipients; D000666:Amphotericin B
keywords: Amphotericin B; antifungal activity; intestinal absorption; lipid-based formulation; oral administration; tropical stability