Local pulmonary drug delivery in the preterm rabbit: feasibility and efficacy of daily intratracheal injections
Journal
American Journal of Physiology-Lung Cellular and Molecular Physiology
ISSN
1040-0605
1522-1504
Date Issued
2019
Author(s)
Thomas Salaets
André Gie
Margo Aertgeerts
Olivier Gheysens
Greetje Vande Velde
Michel Koole
Xabi Murgia
Costanza Casiraghi
Francesca Ricci
Fabrizio Salomone
Gino Villetti
Karel Allegaert
Jan Deprest
Jaan Toelen
Type
Resource Types::text::journal::journal article
URL Institutional Repository
Abstract
<jats:p> Recent clinical trials in newborns have successfully used surfactant as a drug carrier for an active compound, to minimize systemic exposure. To investigate the translational potential of surfactant-compound mixtures and other local therapeutics, a relevant animal model is required in which intratracheal administration for maximal local deposition is technically possible and well tolerated. Preterm rabbit pups (born at 28 days of gestation) were exposed to either hyperoxia or normoxia and randomized to receive daily intratracheal surfactant, daily intratracheal saline, or no injections for 7 days. At day 7, the overall lung function and morphology were assessed. Efficacy in terms of distribution was assessed by micro-PET-CT on both day 0 and day 7. Lung function as well as parenchymal and vascular structure were altered by hyperoxia, thereby reproducing a phenotype reminiscent of bronchopulmonary dysplasia (BPD). Neither intratracheal surfactant nor saline affected the survival or the hyperoxia-induced BPD phenotype of the pups. Using PET-CT, we demonstrate that 82.5% of the injected radioactive tracer goes and remains in the lungs, with a decrease of only 4% after 150 min. Surfactant and saline can safely and effectively be administered in spontaneously breathing preterm rabbits. The described model and method enable researchers to evaluate intratracheal pharmacological interventions for the treatment of BPD. </jats:p>
Subjects
bronchopulmonary dysplasia
;
intratracheal administration
;
local drug delivery
;
preterm rabbit
;
surfactant
;
animals
;
animals, newborn
;
bronchopulmonary dysplasia
;
disease models, animal
;
drug delivery systems
;
feasibility studies
;
female
;
humans
;
infant, newborn
;
injections
;
lung
;
positron emission tomography computed tomography
;
pregnancy
;
premature birth
;
pulmonary surfactants
;
rabbits
;
trachea
;
treatment outcome
;
poractant
;
sodium chloride
;
surfactant
;
lung surfactant
;
airway resistance
;
animal experiment
;
animal model
;
article
;
birth weight
;
body weight
;
controlled study
;
drug delivery system
;
drug efficacy
;
inspiratory capacity
;
lung dysplasia
;
lung function
;
micro-computed tomography
;
mortality
;
nonhuman
;
positron emission tomography-computed tomography
;
priority journal
;
respiratory distress
;
total lung capacity
;
animal
;
diagnostic imaging
;
disease model
;
drug effect
;
feasibility study
;
female
;
human
;
injection
;
leporidae
;
lung
;
lung dysplasia
;
newborn
;
pathophysiology
;
pregnancy
;
prematurity
;
trachea
;
treatment outcome