Differential behaviour of fluid liposomes toward mammalian epithelial cells and bacteria: restriction of fusion to bacteria.

摘要

Previous work demonstrated that fluid liposomes developed in our laboratory are able to fuse with bacterial outer membranes. This fusion improved the penetration and activity of liposome-encapsulated antibiotics and antisense oligonucleotides into the bacterial cells. Because it is anticipated that fluid liposome encapsulated antibiotics will be administered by aerosols to patients with chronic pulmonary infections or cystic fibrosis (CF), we conducted comparative studies in E. coli, P. aeruginosa and human lung epithelial cells using lipid-mixing assays to investigate the possibility that fluid liposomes might fuse with surrounding epithelial cells. After a 2 h incubation at 4 and 37 degrees C, no fusion between fluid liposomes and human lung epithelial cells was observed, whereas mean levels of 71 and 37% of fusion were observed at 37 degrees C with E. coli and P. aeruginosa cells, respectively. No fusion was observed at 4 degrees C in any cells. A kinetic study where temperature was gradually increased from 7 to 37 degrees C indicated that the fusion process in the two bacteria starts between 28 and 31 degrees C with a mean fusion rate of 0.60%/min at 31 degrees C to reach 1.18%/min at 37 degrees C. The present work suggests that it is unlikely that fluid liposomes fuse with host cells lining the human respiratory tract and further elucidates the fusogenic properties of fluid liposomes with respect to prokaryotes and eukaryotes.