Bacteriophage-Loaded Nanostructured Lipid Carrier: Improved Pharmacokinetics Mediates Effective Resolution ofKlebsiella pneumoniae–Induced Lobar Pneumonia

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.

Effects of storage conditions on the stability of spray dried, inhalable bacteriophage powders

“…Similar results were reported in Pabary et al (2016). Singla et al (2015) compared the efficacy of intraperitoneal application of phages alone and when delivered in liposomes in a mouse model of K. pneumoniae lobar pneumonia. While the phages alone treatment was only able to prevent the infection up to 6 h prior to bacterial challenge, the liposome-entrapped phages provided complete protection up to 48 h prior treatment.…”

“…With these increased research efforts, a large number of novel phages have been isolated and characterised to target broad-spectrum antimicrobial resistance of Pseudomonas aeruginosa , Staphylocccus aureus and Burkholderia cepacia complex ( BCC ) (Ackermann, 2007; Larche et al, 2012; Essoh et al, 2013), which are major pathogens in chronically infected cystic fibrosis (CF) patients. In addition, the potential of phages to treat respiratory infections caused by MDR bacteria has recently been demonstrated in animal models (Chhibber et al, 2008; Carmody et al, 2010; Debarbieux et al, 2010; Morello et al, 2011; Alemayehu et al, 2012; Semler et al, 2014; Singla et al, 2015; Cao et al, 2015; Pabary et al, 2016). These promising results have made phage therapy one of the most promising alternatives to conventional antibiotics for respiratory infectious diseases.…”

Phage therapy of pulmonary infections

“…Exceptional were the mouse studies by Chhibber et al, 60 Semler et al, 62 and Singla et al 61 which also tested intraperitoneal phage application. Clinical treatments, by contrast, involved a diversity of approaches to phage application including more or less direct injection, 28,38 puncture, 28,40,41 or catheterization 40 into or into the vicinity of infections as well as parenteral application including intravenous.…”

“…Singla et al 61 packaged phages within liposomes for intraperitoneal delivery in the treatment of experimental mouse K. pneumonia-associated lobar pneumonia. Substantial bacterial clearance was observed without treatment by 72 h post intranasal challenge with 10 4 CFU.…”

Therapeutic bacteriophages as a rescue treatment for drug‐resistant infections – anin vivostudies overview

“…Liposome‐encapsulated bacteriophages were administered after 2–3 days. A reduction in the bacterial titre was observed in the bacteriophage‐treated mice; the degree of reduction was also dependent on the time between infection and bacteriophage administration (Singla et al ).…”