Bacteriophage-loaded nanostructured lipid carrier: improved pharmacokinetics mediates effective resolution of Klebsiella pneumoniae-induced lobar pneumonia

J Infect Dis. 2015 Jul 15;212(2):325-34. doi: 10.1093/infdis/jiv029. Epub 2015 Jan 20.

Abstract

This study examined the therapeutic and prophylactic potential of bacteriophages in a mouse model of Klebsiella pneumoniae lobar pneumonia. Phages were administered intraperitoneally. Liposome-entrapped phages (LP) were effective in treating infection, even when therapy was delayed by 3 days after the induction of pneumonia. In contrast, nonliposomal phages provided protection when administered 24 hours after infection. Administration of nonliposomal phages 6 hours prior to intranasal bacterial challenge resulted in complete protection, compared with LP, which was effective even when administered 48 hours prior to infection. Increased reduction and a greater increment in the levels of proinflammatory and antiinflammatory cytokines, respectively, in homogenates of lung from LP-treated mice were suggestive of increased efficacy of LP in the treatment of pneumonia. This is the first study to assess liposomes as a delivery vehicle for phage, and the results confirm the superiority of LP for both therapeutic and prophylactic applications.

Keywords: K. pneumoniae; liposome entrapped phages; phage therapy; prophylaxis; therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteriophages / physiology*
  • Female
  • Inflammation Mediators / metabolism
  • Klebsiella Infections / immunology
  • Klebsiella Infections / microbiology
  • Klebsiella Infections / therapy*
  • Klebsiella pneumoniae / virology*
  • Liposomes
  • Lung / immunology
  • Lung / metabolism
  • Lung / microbiology
  • Mice, Inbred BALB C
  • Nanostructures / administration & dosage*
  • Pneumonia, Bacterial / immunology
  • Pneumonia, Bacterial / microbiology
  • Pneumonia, Bacterial / therapy*

Substances

  • Inflammation Mediators
  • Liposomes