Liposomal bismuth-ethanedithiol formulation enhances antimicrobial activity of tobramycin.
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.
Halwani
Majed
M
The Novel Drug & Vaccine Delivery Systems Facility, Department of Chemistry and Biochemistry, Laurentian University, 935 Ramsey Lake Road, Sudbury, Ontario, Canada.
Blomme
Shanna
S
Suntres
Zacharias E
ZE
Alipour
Misagh
M
Azghani
Ali O
AO
Kumar
Aseem
A
Omri
Abdelwahab
A
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*
D000900:Anti-Bacterial Agents; D003470:Culture Media; D004337:Drug Carriers; D008081:Liposomes; D008623:Mercaptoethanol; C031854:1,2-ethanedithiol; D014031:Tobramycin