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Absence of lung fibrosis after a single pulmonary delivery of lipid nanocapsules in rats

Abstract : Lipid nanocapsules (LNCs) are potential drug carriers for pulmonary delivery since they can be nebulized without any structural or functional changes, and the aerosols produced are highly compatible with pulmonary drug delivery in human beings. The alveolar surface tension, in vitro cytotoxicity, biodistribution and pulmonary toxicity in rats of a single endotracheal spray of LNCs or paclitaxel-loaded LNCs were studied. In vitro cytotoxicity of LNCs after a spray remained unchanged. Biodistribution study showed a homogeneous repartition in the lungs in rats with an improvement in lung retention of the radiolabeled tracer loaded in LNCs compared to the absence of LNCs with a lung half-time of 8.8±0.7 hours. Bronchoalveolar fluid analysis revealed transient 7-day alveolar inflammation, reaching a maximum between days 2 and 4, characterized by a peak of granulocytes at day 1 followed by a peak of lymphocytes at day 3. Alveolar protein levels were increased at days 3 and 7. Acute inflammation was increased with paclitaxel-loaded LNCs in comparison with blank LNCs but dropped out at day 7. No histological pulmonary lesion was observed at day 60. LNCs lowered surface tension to a greater degree than Curosurf® in a physicochemical model of the pulmonary alveolus. A single pulmonary delivery of LNCs induces a short-term alveolar inflammation with no residual lesions in rats at day 60. These data permit to start the study of LNCs in surfactant replacement therapy.
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Submitted on : Tuesday, June 12, 2018 - 2:02:09 PM
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José Hureaux, Franck Lacœuille, Frédéric Lagarce, Marie-Christine Rousselet, Aurélien Contini, et al.. Absence of lung fibrosis after a single pulmonary delivery of lipid nanocapsules in rats. International Journal of Nanomedicine, Dove Medical Press, 2017, 12, pp.8159 - 8170. ⟨10.2147/IJN.S146740⟩. ⟨inserm-01813483⟩



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