Therapeutic efficacy of aerosolized liposome-encapsulated nubiotic against pulmonaryPseudomonas aeruginosainfection

Abstract

Respiratory tract infection caused by Pseudomonas aeruginosa is one of the major causes of mortality and morbidity in cystic fibrosis patients. However, physicians treating cystic fibrosis patients are confronting the growing problem of multiple-drug resistance in P. aeruginosa. Nubiotics are a novel class of nucleotide-based drugs that have the potential to improve clinical outcome against pulmonary infection by multidrug resistant P. aeruginosa. In this study, therapeutic efficacy of liposome-encapsulated nubiotic (Nu-3, a protonated deoxyribonucleotide-based antibiotic) was evaluated using a rat model of pulmonary P. aeruginosa infection. Nu-3 was loaded into small unilamellar vesicles using a remote loading procedure. Groups of Sprague–Dewley rats were infected intratracheally with cystic fibrosis strains of P. aeruginosa, which were enmeshed in agar beads (2–10 × 106 enmeshed bacteria/animal). At 2 weeks postinfection, the infected rats were treated with a single-exposure dose of liposome-encapsulate...