title: Efficacy of an oral and tropically stable lipid-based formulation of Amphotericin B (iCo-010) in an experimental mouse model of systemic candidiasis.
abstract: OBJECTIVE
  An oral lipid based formulation that exhibits tropical stability (iCo-010) was developed to enhance the absorption of orally administered amphotericin B (AmB). iCo-010 has previously shown high efficacy in an acute model of systemic candidiasis in rats, directing the focus of this study to be its efficacy in a chronic model of systemic candidiasis in mice.
  
  
  METHODS
  Mice were infected with 0.6 to 1×108 CFUs of Candida albicans ATCC 18804 strain by tail vein injection and were left for three days to develop the infection after which time treatment was initiated. The infected animals were assigned to the following treatment groups: no treatment (control) or iCo-010 at 5, 10 and 20 mg/kg administered by oral gavage once daily (QD) for 5 consecutive days. The animals were sacrificed 7 days after the last dose and the concentration of AmB and the fungal burden were assessed within the liver, kidneys, heart, lungs, spleen and brain.
  
  
  RESULTS
  Although the infection was relatively low (~ 60-100 CFUs/ 1 ml tissue homogenate) in the liver, lungs and heart, the infection level was very high (70 000 CFUs / 1 ml tissue homogenate) in the kidney tissues for the control group. The highest concentrations of AmB were recovered in the kidneys and the spleen. The fungal burden in the tissues was lowered by 69-96% in the treatment groups when compared to the control group.
  
  
  CONCLUSIONS
  Oral iCo-010 is an effective treatment of systemic candidiasis in the mouse model.
authors.forename: Fady
authors.initials: F
authors.lastname: Ibrahim
authors.forename: Olena
authors.initials: O
authors.lastname: Sivak
authors.forename: Ellen K
authors.initials: EK
authors.lastname: Wasan
authors.forename: Karen
authors.initials: K
authors.lastname: Bartlett
authors.affiliation: Faculty of Pharmaceutical Sciences, The University of British Columbia, 2405 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada. Kishor.Wasan@ubc.ca.
authors.forename: Kishor M
authors.initials: KM
authors.lastname: Wasan
mesh_terms: D000284:Administration, Oral; D000666:Amphotericin B / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development; D002177:Candidiasis / Q000188:drug therapy* / Q000382:microbiology; D015169:Colony Count, Microbial; D004305:Dose-Response Relationship, Drug; D004339:Drug Compounding; D006321:Heart / Q000187:drug effects / Q000382:microbiology; D007668:Kidney / Q000187:drug effects / Q000382:microbiology; D008099:Liver / Q000187:drug effects / Q000382:microbiology; D008168:Lung / Q000187:drug effects / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009829:Oleic Acids / Q000737:chemistry; D009928:Organ Specificity; D011092:Polyethylene Glycols / Q000737:chemistry; D013154:Spleen / Q000187:drug effects / Q000382:microbiology; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D009829:Oleic Acids; C482692:Peceol; C104509:gelucire 44-14; D011092:Polyethylene Glycols; D000666:Amphotericin B