A liposome model to treat pseudomonas in lungs of cystic fibrosis and immune compromised patients.

Pseudomonas aeruginosa (P. aeruginosa) an opportunistic, deadly gram-negative bacterium, occurs in patients with cystic fibrosis and is a major cause of death for patients with neutropenia or ones who have suffered critical burns. There are a number of distinctive features in the lungs of affected patients that need to be addressed: P. aeruginosa (1) secretes a phospholipase C that lyses red cells and degrades pulmonary surfactant; (2) secretes an elastase that degrades IgG s and extra cellular matrix proteins and therefore may enhance tissue invasion; (3) secretes iron-containing compounds that are highly toxic to endothelial cells; (4) has proteins and pili that enable it to adhere to lung epithelial cells; and (5) produces a mucoid polysaccharide that anchors the cells. Styx liposomes can be engineered and delivered to the lung by inhalation so they will: (a) be resistant to uptake by alveolar macrophages allowing them to act in the alveolar space; (b) provide phospholipids as a competitive substrate for the extracellular Pseudomonas phospholipase C; (c) contain competitive inhibitors of phospholipase C; (d) contain iron chelators to reduce the effects of the toxic iron-containing molecules released by Pseudomonas; (e) contain antibiotics active against the Pseudomonas infection; and (f) contain antimucolytic compounds. Approaches (a) and (b) will reduce the destructive action of phospholipase C on surfactant and epithelial cell membranes. Further, degradation of liposomes by pseudomonas phospholipase C should be able to target the release of (b), (c), (d), (e) and (f) at the site of infection.