Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Physiology, Respiratory System, bronchopulmonary dysplasia, intratracheal administration, local drug delivery, preterm rabbit, surfactant, BRONCHOPULMONARY DYSPLASIA, RESPIRATORY-DISTRESS, PORACTANT ALPHA, PREMATURE LAMBS, ANIMAL-MODELS, LUNG INJURY, IN-VITRO, SURFACTANT, BUDESONIDE, INFANTS, 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, C24/17/061#54270844, 0606 Physiology, 1116 Medical Physiology, 3201 Cardiovascular medicine and haematology, 3208 Medical physiology

Abstract:

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.