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

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journal contribution
posted on 04.06.2021, 15:49 by Sebastian Vencken, Camilla Foged, Joanne M Ramsey, Louise Sweeney, Sally-Ann CryanSally-Ann Cryan, Ronan J MacLoughlin, Catherine GreeneCatherine Greene
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.

Funding

National Children’s Research Centre (C/13/1)

Cystic Fibrosis Foundation Therapeutics (GREENE15XXO)

Science Foundation Ireland Industrial Fellowship and Investigators Program (13/IA/1840)

History

Comments

The original article is available at https://openres.ersjournals.com

Published Citation

Vencken S, Foged C, Ramsey JM, Sweeney L, Cryan SA, MacLoughlin RJ, Greene CM. Nebulised lipid-polymer hybrid nanoparticles for the delivery of a therapeutic anti-inflammatory microRNA to bronchial epithelial cells. ERJ Open Res. 2019;5(2):00161-2018.

Publication Date

8 April 2019

PubMed ID

30972350

Department/Unit

  • Anatomy and Regenerative Medicine
  • Beaumont Hospital
  • Clinical Microbiology
  • RCSI Tissue Engineering Group (TERG)
  • School of Pharmacy and Biomolecular Sciences
  • Cu00daRAM Centre for Research in Medical Devices

Research Area

  • Respiratory Medicine
  • Chemistry and Pharmaceutical Sciences
  • Biomaterials and Regenerative Medicine
  • Immunity, Infection and Inflammation

Publisher

European Respiratory Society (ERS)

Version

  • Published Version (Version of Record)