Natural Derived Surfactant Preparation As a Carrier of Polymyxin E for Treatment of Pseudomonas aeruginosa Pneumonia in a Near-Term Rabbit Model

Abstract

Background: Pulmonary surfactant spreads rapidly over the airway epithelium, a property that could be harnessed to transport drugs into the lungs. For efficient drug delivery, an interaction between pulmonary surfactant and the drug to be administered is likely needed. On the other hand, the interaction should not compromise the activity of surfactant or the drug once delivered in vivo. The antibiotics gentamicin (an aminoglycoside) and polymyxin E represent drugs that could benefit from being delivered directly to the lung, thereby increasing local concentrations and reducing systemic side effects. Our aim was to study how the animal-derived surfactant poractant alfa (Curosurf((R))) affects the activities of polymyxin E and gentamicin against Pseudomonas aeruginosa. Methods:In vitro antimicrobial assays and a neonatal near-term rabbit model were used to evaluate the combinations of antibiotics and surfactant against Pseudomonas aeruginosa. Results: The bactericidal activity of polymyxin E, but not of gentamicin, against P. aeruginosa was partly reduced in vitro in the presence of poractant alfa. In contrast, in the rabbit model of P. aeruginosa pneumonia, polymyxin E administrated together with surfactant was superior in lowering the bacterial load in the lungs compared to polymyxin E alone, without affecting plethysmographically recorded lung compliance. Conclusions: The results suggest that polymyxin E interacts with poractant alfa, which reduces the antibacterial effect in vitro. However, when polymyxin E mixed with surfactant is used in the in vivo pneumonia model, increased bactericidal effect was observed. This may be due to a more efficient spreading mediated by interactions between polymyxin E and surfactant. These results warrant further studies of surfactant preparations for drug delivery against lung infections.

Keywords

bacterial infection; drug delivery; gentamicin; polymyxin E; pulmonary surfactant

Published in

Journal of Aerosol Medicine and Pulmonary Drug Delivery
2019, volume: 32, number: 2, pages: 110-118
Publisher: MARY ANN LIEBERT, INC

SLU Authors

• Rising, Anna

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    
  • Karolinska Institute

UKÄ Subject classification

Pharmaceutical Sciences

Publication identifier

• DOI: https://doi.org/10.1089/jamp.2018.1468

Permanent link to this page (URI)

https://res.slu.se/id/publ/96930