TY - JOUR
T1 - Natural derived surfactant preparation as a carrier of Polymyxin e for treatment of pseudomonas aeruginosa pneumonia in a near-term rabbit model
AU - Basabe-Burgos, Oihana
AU - Zebialowicz, Jakub
AU - Stichtenoth, Guido
AU - Curstedt, Tore
AU - Bergman, Peter
AU - Johansson, Jan
AU - Rising, Anna
N1 - Funding Information:
We thank Marie Haegerstrand-Björkman and Bim Lin-derholm for technical assistance. The work was supported by the following grants; Swedish Research Council (2014– 2408), Center for innovative medicine (CIMED), and FORMAS (2015-629), Chiesi Farmaceutici, Parma, Italy.
Funding Information:
The authors of this article obtained financial support from Chiesi Farmaceutici, Parma, Italy.
Publisher Copyright:
© 2019, Mary Ann Liebert, Inc.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2019/4
Y1 - 2019/4
N2 - 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®) 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.
AB - 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®) 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.
UR - http://www.scopus.com/inward/record.url?scp=85056463097&partnerID=8YFLogxK
U2 - 10.1089/jamp.2018.1468
DO - 10.1089/jamp.2018.1468
M3 - Journal articles
C2 - 30339061
AN - SCOPUS:85056463097
SN - 1941-2711
VL - 32
SP - 110
EP - 118
JO - Journal of Aerosol Medicine and Pulmonary Drug Delivery
JF - Journal of Aerosol Medicine and Pulmonary Drug Delivery
IS - 2
ER -