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LOCAL PULMONARY DRUG DELIVERY IN THE PRETERM RABBIT: FEASIBILITY AND EFFICACY OF DAILY INTRATRACHEAL INJECTIONS.

Recent clinical trials in newborns have successfully used surfactant as a drug carrier for an active compound, in order to minimize systemic exposure. To investigate the translational potential of surfactant-compound mixtures and other local therapeutics, a relevant animal model is required where intratracheal (IT) 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 IT surfactant, daily IT 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 microPET-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 BPD. Neither IT 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 radio-active tracer goes and remains into the lungs, with a decrease of only 4% after 150 minutes. Surfactant and saline can safely and effectively be administered in spontaneously breathing preterm rabbits. The described model and method enable researchers to evaluate IT pharmacological interventions for the treatment of BPD.

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