2. Abstract ofInvention, Technology, or Copyrightable Material: Polymyxin B is a polypeptide antibiotic increasingly used as the last treatment for multidrug resistant Gram-negative bacterial infections. Despite excellent in vitro antimicrobial activity against many Gram-negative bacteria, the clinical efficacy in severe respiratory tract infections (e.g., pneumonia) is not very favorable, likely due to the limited drug exposure achieved in the site of infection (i.e., epithelial lining fluid). On the other hand, considerable dose escalation to improve efficacy is hindered by concerns of nephrotoxicity. We have developed a liposomal formulation of polymyxin B, which has been shown to have: (1) enhanced drug delivery in epithelial lining fluid and (2) better treatment efficacy in a neutropenic murine pneumonia model. Two groups of neutropenic mice (n=6) were infected with a clinical strain of Pseudomonas aeruginosa, and treated with intravenous polymyxin B liposome or aqueous solution at 3 mg/kg every 6 hour for up to 24 hours. Approximately 3 times the drug exposure in the epithelial lining fluid was achieved in the liposomal group, compared to the aqueous solution group. In addition, a significantly lower bacterial burden was seen in the liposomal group (3.0 ± 0.5 vs. 7.8 ± 0.9 Log CFU/g) after the treatment. Treatment with a polymyxin B liposomal formulation yielded higher penetration into pulmonary epithelial lining fluid, which resulted in more favorable efficacy. Potential clinical application of idea: a novel drug formulation would offer a higher treatment effectiveness without a significant compromise of its toxicity potential.