TY - JOUR T1 - Nebulised lipid–polymer hybrid nanoparticles for the delivery of a therapeutic anti-inflammatory microRNA to bronchial epithelial cells JF - ERJ Open Research JO - erjor DO - 10.1183/23120541.00161-2018 VL - 5 IS - 2 SP - 00161-2018 AU - Sebastian Vencken AU - Camilla Foged AU - Joanne M. Ramsey AU - Louise Sweeney AU - Sally-Ann Cryan AU - Ronan J. MacLoughlin AU - Catherine M. Greene Y1 - 2019/04/01 UR - http://openres.ersjournals.com/content/5/2/00161-2018.abstract N2 - Modulation of microRNAs (miRNAs), endogenous regulators of gene expression, is a promising strategy for tackling inflammatory lung diseases. In this proof-of-concept study, we tested delivery of miR-17 to bronchial epithelial cells (BECs) using nebulised lipid–polymer hybrid nanoparticles (LPNs). The primary aim was to reduce the induced secretion of miR-17's target, i.e. the pro-inflammatory chemokine interleukin (IL)-8.Synthetic miR-17 mimics were loaded into LPNs composed of poly(dl-lactic-co-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.The z-average, polydispersity index and ζ-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 >40% in BECs.This study suggests that DOTAP-modified PLGA LPNs are efficient and well-tolerated carriers for delivery of miRNA mimics to BECs.Nebulised miR-17-loaded DOTAP–PLGA nanoparticles are suitable, nontoxic carriers for knockdown of IL-8 in bronchial epithelial cells and form a platform upon which future miRNA-based therapeutics could be developed for inflammatory lung disease http://ow.ly/5iT330nSNZI ER -