title: Supramolecular assemblies of rifampicin and cationic bilayers: preparation, characterization and micobactericidal activity.
abstract: BACKGROUND
  Cationic bilayers based on the inexpensive synthetic lipid dioctadecyldimethylammonium bromide (DODAB) have been useful as carriers for drug delivery, immunoadjuvants for vaccines and active antimicrobial agents.
  
  
  METHODS
  Rifampicin (RIF) or isoniazid (ISO) interacted with DODAB bilayer fragments (BF) or large vesicles (LV). Dispersions were evaluated by dynamic light-scattering for zeta-average diameter (Dz) and zeta-potential (ζ) analysis; dialysis for determination of drug entrapment efficiency; plating and CFU counting for determination of cell viability of Mycobacterium smegmatis or tuberculosis, minimal bactericidal concentration (MBC) and synergism index for DODAB/drug combinations.
  
  
  RESULTS
  DODAB alone killed micobacteria over a range of micromolar concentrations. RIF aggregates in water solution were solubilised by DODAB BF. RIF was incorporated in DODAB bilayers at high percentiles in contrast to the leaky behavior of ISO. Combination DODAB/RIF yielded MBCs of 2/2 and 4/0.007 μg/mL against Mycobacterium smegmatis or Mycobacterium tuberculosis, respectively. Synergism indexes equal to 0.5 or 1.0, indicated synergism against the former and independent action, against the latter species.
  
  
  CONCLUSIONS
  In vitro, DODAB acted effectively both as micobactericidal agent and carrier for rifampicin. The novel assemblies at reduced doses may become valuable against tuberculosis.
authors.affiliation: Biocolloids Lab, Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, CP 26077, CEP 05513-970, São Paulo SP, Brazil.
authors.forename: Lilian
authors.initials: L
authors.lastname: Barbassa
authors.forename: Elsa M
authors.initials: EM
authors.lastname: Mamizuka
authors.forename: Ana M
authors.initials: AM
authors.lastname: Carmona-Ribeiro
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology; D000904:Antibiotics, Antitubercular / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers; D004339:Drug Compounding / Q000379:methods; D004357:Drug Synergism; D008051:Lipid Bilayers / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects*; D015394:Molecular Structure; D020102:Mycobacterium smegmatis / Q000187:drug effects / Q000254:growth & development; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000254:growth & development; D000644:Quaternary Ammonium Compounds / Q000737:chemistry / Q000494:pharmacology*; D012293:Rifampin / Q000737:chemistry / Q000494:pharmacology*; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D000904:Antibiotics, Antitubercular; D004337:Drug Carriers; D008051:Lipid Bilayers; D000644:Quaternary Ammonium Compounds; C015831:dimethyldioctadecylammonium; D012293:Rifampin