Nebulised lipid-polymer hybrid nanoparticles for the delivery of a therapeutic anti-inflammatory microRNA to bronchial epithelial cells.

摘要: Modulation of microRNAs (miRNAs), endogenous regulators gene expression, is a promising strategy for tackling inflammatory lung diseases. In this proof-of-concept study, we tested delivery miR-17 to bronchial epithelial cells (BECs) using nebulised lipid-polymer hybrid nanoparticles (LPNs). The primary aim was reduce the induced secretion miR-17's target, i.e. pro-inflammatory chemokine interleukin (IL)-8. Synthetic mimics were loaded into LPNs composed poly(dl-lactic-co-glycolic acid) (PLGA) and cationic lipid 1,2-dioleoyloxy-3-(trimethylammonium)propane (DOTAP) double emulsion solvent evaporation method Aerogen Solo nebuliser. physicochemical, aerosol, cytotoxic properties characterised. effect on lipopolysaccharide (LPS)-induced IL-8 production from human NuLi-1 BECs by ELISA. z-average, polydispersity index ζ-potential aerodynamic suspensions in range optimal deposition bronchi bronchioles post-inhalation. Cytotoxic effects minimal with model cargo. Nebulisation did not affect physicochemical or functional LPNs. Nebulised miR-17-loaded downregulated LPS-induced >40% BECs. This study suggests that DOTAP-modified PLGA are efficient well-tolerated carriers miRNA