title: Liposomal bismuth-ethanedithiol formulation enhances antimicrobial activity of tobramycin.
abstract: Pseudomonas aeruginosa and Burkholderia cenocepacia (formally, genomovar III genotype of Burkholderia cepacia complex) have emerged as serious opportunistic resistant pathogens in patients with cystic fibrosis (CF). We have developed a liposomal formulation containing bismuth-ethanedithiol (BiEDT) and tobramycin to overcome bacterial resistance. The stability of liposomal BiEDT-tobramycin (LipoBiEDT-TOB) was studied in phosphate buffered saline (PBS) and human pooled plasma at 4 and 37 degrees C. Minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) for free tobramycin and LipoBiEDT-TOB against clinical isolates of P. aeruginosa and B. cenocepacia were determined by the broth dilution method. The toxicity profile and the influence on bacterial adhesion of LipoBiEDT-TOB formulation were determined using a human lung carcinoma cell line (A549). LipoBiEDT-TOB exhibited lower MICs than the conventional antibiotic (0.25mg/L vs. 1024 mg/L) and eradicated this highly resistant bacterial strain of P. aeruginosa (PA-48913) at very low concentrations (4 mg/L vs. 4096 mg/L). LipoBiEDT-TOB was significantly less toxic when compared to the free BiEDT, as evaluated by the MTT and LDH assay. The LipoBiEDT-TOB formulation suppressed bacterial adhesion (B. cenocepacia M13642R) to A549 cells. These data suggest that the novel LipoBiEDT-TOB drug delivery system could be utilized as a new strategy to enhance the efficacy of existing antibiotics against resistant organisms that commonly affect individuals with chronic lung infections.
authors.affiliation: The Novel Drug & Vaccine Delivery Systems Facility, Department of Chemistry and Biochemistry, Laurentian University, 935 Ramsey Lake Road, Sudbury, Ontario, Canada.
authors.forename: Majed
authors.initials: M
authors.lastname: Halwani
authors.forename: Shanna
authors.initials: S
authors.lastname: Blomme
authors.forename: Zacharias E
authors.initials: ZE
authors.lastname: Suntres
authors.forename: Misagh
authors.initials: M
authors.lastname: Alipour
authors.forename: Ali O
authors.initials: AO
authors.lastname: Azghani
authors.forename: Aseem
authors.initials: A
authors.lastname: Kumar
authors.forename: Abdelwahab
authors.initials: A
authors.lastname: Omri
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D001422:Bacterial Adhesion / Q000187:drug effects; D016956:Burkholderia cepacia / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D003470:Culture Media; D004337:Drug Carriers; D004355:Drug Stability; D006801:Humans; D008081:Liposomes; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008623:Mercaptoethanol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D014031:Tobramycin / Q000008:administration & dosage* / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D003470:Culture Media; D004337:Drug Carriers; D008081:Liposomes; D008623:Mercaptoethanol; C031854:1,2-ethanedithiol; D014031:Tobramycin