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Local pulmonary drug delivery in the preterm rabbit: feasibility and efficacy of daily intratracheal injections.
Salaets, Thomas; Gie, André; Jimenez, Julio; Aertgeerts, Margo; Gheysens, Olivier; Vande Velde, Greetje; Koole, Michel; Murgia, Xabi; Casiraghi, Costanza; Ricci, Francesca; Salomone, Fabrizio; Villetti, Gino; Allegaert, Karel; Deprest, Jan; Toelen, Jaan.
Afiliação
  • Salaets T; Department of Development and Regeneration, Cluster Woman and Child, KU Leuven , Leuven , Belgium.
  • Gie A; Department of Development and Regeneration, Cluster Woman and Child, KU Leuven , Leuven , Belgium.
  • Jimenez J; Department of Development and Regeneration, Cluster Woman and Child, KU Leuven , Leuven , Belgium.
  • Aertgeerts M; Facultad de Medicina, Universidad del Desarollo, Clínica Alemana, Santiago de Chile, Chile.
  • Gheysens O; Department of Development and Regeneration, Cluster Woman and Child, KU Leuven , Leuven , Belgium.
  • Vande Velde G; Department of Imaging and Pathology, KU Leuven , Leuven , Belgium.
  • Koole M; Department of Imaging and Pathology, KU Leuven , Leuven , Belgium.
  • Murgia X; Department of Imaging and Pathology, KU Leuven , Leuven , Belgium.
  • Casiraghi C; Department of Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland , Saarbrücken , Germany.
  • Ricci F; R&D Department, Chiesi Farmaceutici, Parma , Italy.
  • Salomone F; R&D Department, Chiesi Farmaceutici, Parma , Italy.
  • Villetti G; R&D Department, Chiesi Farmaceutici, Parma , Italy.
  • Allegaert K; R&D Department, Chiesi Farmaceutici, Parma , Italy.
  • Deprest J; Department of Development and Regeneration, Cluster Woman and Child, KU Leuven , Leuven , Belgium.
  • Toelen J; Division of Neonatology, Department of Pediatrics, Erasmus MC Sophia Children's Hospital , Rotterdam , The Netherlands.
Am J Physiol Lung Cell Mol Physiol ; 316(4): L589-L597, 2019 04 01.
Article em En | MEDLINE | ID: mdl-30675804
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Surfactantes Pulmonares / Displasia Broncopulmonar / Sistemas de Liberação de Medicamentos Tipo de estudo: Clinical_trials Limite: Animals / Female / Humans / Newborn / Pregnancy Idioma: En Revista: Am J Physiol Lung Cell Mol Physiol Assunto da revista: BIOLOGIA MOLECULAR / FISIOLOGIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Bélgica

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Surfactantes Pulmonares / Displasia Broncopulmonar / Sistemas de Liberação de Medicamentos Tipo de estudo: Clinical_trials Limite: Animals / Female / Humans / Newborn / Pregnancy Idioma: En Revista: Am J Physiol Lung Cell Mol Physiol Assunto da revista: BIOLOGIA MOLECULAR / FISIOLOGIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Bélgica