Local pulmonary drug delivery in the preterm rabbit: feasibility and efficacy of daily intratracheal injections

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dc.contributor.authorSalaets, Thomas
dc.contributor.authorGie, Andre
dc.contributor.authorJiménez, Julio
dc.contributor.authorAertgeerts, Margo
dc.contributor.authorGheysens, Olivier
dc.contributor.authorVande Velde, Vande Velde
dc.contributor.authorKoole, Michel
dc.contributor.authorMurgia, Xabi
dc.contributor.authorCasiraghi, Costanza
dc.contributor.authorRicci, Francesca
dc.contributor.authorSalomone, Fabrizio
dc.contributor.authorVilletti, Gino
dc.contributor.authorAllegaert, Karel
dc.contributor.authorDeprest, Jan
dc.contributor.authorToelen, Jaan
dc.date.accessioned2020-08-31T20:00:20Z
dc.date.available2020-08-31T20:00:20Z
dc.date.issued2019-04
dc.description.abstractRecent 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.es
dc.identifier.citationAm J Physiol Lung Cell Mol Physiol . 2019 Apr 1;316(4):L589-L597. doi: 10.1152/ajplung.00255.2018.es
dc.identifier.urihttps://doi.org/10.1152/ajplung.00255.2018es
dc.identifier.urihttp://hdl.handle.net/11447/3386
dc.language.isoenes
dc.publisherAmerican Physiological Societyes
dc.subjectBronchopulmonary dysplasiaes
dc.subjectIntratracheal administrationes
dc.subjectLocal drug deliveryes
dc.subjectPreterm rabbites
dc.subjectSurfactant.es
dc.titleLocal pulmonary drug delivery in the preterm rabbit: feasibility and efficacy of daily intratracheal injectionses
dc.typePreprintes

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