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

Authors Hureaux J, Lacoeuille F, Lagarce F, Rousselet MC, Contini A, Saulnier P, Benoit JP, Urban T

Received 19 July 2017

Accepted for publication 22 September 2017

Published 8 November 2017 Volume 2017:12 Pages 8159—8170


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Thomas Webster

José Hureaux,1,2 Franck Lacœuille,3,4 Frédéric Lagarce,1,5 Marie-Christine Rousselet,6 Aurélien Contini,3,4 Patrick Saulnier,1,7 Jean-Pierre Benoit,1,5 Thierry Urban1,2

1Unité Micro et Nanomédecines Biomimétiques (MINT), Université d’Angers, INSERM 1066, CNRS 6021, Université Bretagne Loire, 2Université d’Angers, CHU, Pôle Hippocrate, Service de Pneumologie, 3Université d’Angers, CHU, Pôle Signal Image Stérilisation, Service de Médecine nucléaire, 4CRCINA, Université Nantes Université Angers, 5Université d’Angers, CHU, Pôle Hippocrate, Pharmacie, 6Université d’Angers, CHU, Pôle de Biologie-Pathologie, Département de Cytologie et d’Histologie Pathologique, 7Université d’Angers, CHU, Service la Recherche Clinique et Innovation, Angers, France

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.

lipid nanocapsules, pulmonary drug delivery, biodistribution, toxicity, paclitaxel

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