title: In vivo activity of a novel amphotericin B formulation with synthetic cationic bilayer fragments.
abstract: Solubilization of amphotericin B (AMB) by dioctadecyldimethylammonium bromide (DODAB) bilayer fragments inspired this evaluation of its in vivo activity from survival and tissue burden experiments against systemic candidiasis in a mouse model. AMB (< or =0.1 g/L) was simply added to a DODAB powder dispersion in water (10 g/L) previously prepared by sonication in the absence of organic solvents. The AMB aggregation state was evaluated from UV-visible light absorption and dynamic light scattering for aggregate sizing. AMB was stabilized by the DODAB bilayer fragments in its monomeric form, mixing of AMB and DODAB dispersion in pure water causing disappearance of large water-insoluble drug aggregates. From survival experiments, both the bilayer, DODAB/AMB, and the traditional deoxycholate/AMB formulation (DOC/AMB) had identical effect when given by the same route at the same dose of 0.4 mg/kg/day given intraperitoneally for 10 days. From spleen and kidneys tissue burden experiments, similar efficacy of both preparations in reducing tissue cfu counts was obtained. In summary, DODAB/AMB was as effective as DOC/AMB for treating systemic candidiasis in a mouse model.
authors.affiliation: Departamento de Análises Clínicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Brazil.
authors.forename: Nilton
authors.initials: N
authors.lastname: Lincopan
authors.forename: Elsa M
authors.initials: EM
authors.lastname: Mamizuka
authors.forename: Ana M
authors.initials: AM
authors.lastname: Carmona-Ribeiro
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use*; D002176:Candida albicans / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy* / Q000382:microbiology; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D003102:Colloids; D015169:Colony Count, Microbial; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D008051:Lipid Bilayers; D051379:Mice; D008826:Microbial Sensitivity Tests; D010316:Particle Size; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D012542:Scattering, Radiation; D013056:Spectrophotometry, Ultraviolet; D016019:Survival Analysis
chemical_list: D000935:Antifungal Agents; D003102:Colloids; D008051:Lipid Bilayers; D000644:Quaternary Ammonium Compounds; C015831:dimethyldioctadecylammonium; D000666:Amphotericin B