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In this proof-of-concept study, we tested delivery of miR-17 to bronchial epithelial cells (BECs) using nebulised lipid\u2013polymer hybrid nanoparticles (LPNs). The primary aim was to reduce the induced secretion of miR-17's target,<jats:italic>i.e.<\/jats:italic>the pro-inflammatory chemokine interleukin (IL)-8.<\/jats:p><jats:p>Synthetic miR-17 mimics were loaded into LPNs composed of poly(<jats:sc>dl<\/jats:sc>-lactic-<jats:italic>co<\/jats:italic>-glycolic acid) (PLGA) and the cationic lipid 1,2-dioleoyloxy-3-(trimethylammonium)propane (DOTAP) using a double emulsion solvent evaporation method and nebulised using the Aerogen Solo nebuliser. The physicochemical, aerosol, inflammatory and cytotoxic properties of LPNs were characterised. The effect of LPNs on lipopolysaccharide (LPS)-induced IL-8 production from human NuLi-1 BECs was tested by ELISA.<\/jats:p><jats:p>The<jats:italic>z<\/jats:italic>-average, polydispersity index and \u03b6-potential of the LPNs and the aerodynamic properties of nebulised suspensions were in a range optimal for deposition in the bronchi and bronchioles post-inhalation. Cytotoxic and pro-inflammatory effects were minimal for LPNs loaded with a model cargo. Nebulisation did not affect the physicochemical or functional properties of the LPNs. Nebulised miR-17-loaded LPNs downregulated LPS-induced IL-8 secretion by &gt;40% in BECs.<\/jats:p><jats:p>This study suggests that DOTAP-modified PLGA LPNs are efficient and well-tolerated carriers for delivery of miRNA mimics to BECs.<\/jats:p>","DOI":"10.1183\/23120541.00161-2018","type":"journal-article","created":{"date-parts":[[2019,4,8]],"date-time":"2019-04-08T14:49:06Z","timestamp":1554734946000},"page":"00161-2018","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":55,"title":["Nebulised lipid\u2013polymer hybrid nanoparticles for the delivery of a therapeutic anti-inflammatory microRNA to bronchial epithelial 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