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Knockdown of Gene Expression in Macrophages by microRNA Mimic-Containing Poly (Lactic-co-glycolic Acid) Microparticles

Department of Medicine, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland
Drug Delivery and Advanced Materials Team, School of Pharmacy, Royal College of Surgeons in Ireland, Dublin 2, Ireland
Centre for Research in Medical Devices (CURAM), RCSI, Dublin and National University of Ireland, Galway H91 HE94, Ireland
Trinity Centre for Bioengineering, Trinity College Dublin, Dublin 2, Ireland
Tissue Engineering Research Group, Royal College of Surgeons in Ireland, 123 St Stephens Green, Dublin 2, Ireland
Lung Biology Group, Department of Clinical Microbiology, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland
Author to whom correspondence should be addressed.
Medicines 2018, 5(4), 133;
Received: 19 November 2018 / Revised: 10 December 2018 / Accepted: 14 December 2018 / Published: 15 December 2018
(This article belongs to the Special Issue Nanoparticle and Liposome based Novel Drug Delivery Systems)
PDF [998 KB, uploaded 15 December 2018]


Background: microRNA (miRNA) regulate target gene expression through translational repression and/or mRNA degradation and are involved in the regulation of inflammation. Macrophages are key inflammatory cells that are important in chronic inflammatory lung diseases such as cystic fibrosis (CF). Macrophage-expressed miRNA represent therapeutic drug targets, yet delivery of nucleic acids to macrophages has proved challenging. Methods: miRNAs were encapsulated in poly (lactic-co-glycolic acid) (PLGA)-based microparticles using double emulsion solvent evaporation and characterised for physicochemical features. Phorbol myristic acetate (PMA)-differentiated U937 macrophages were transfected with empty PLGA microparticles or those encapsulating a premiR-19b-3p or scrambled control miRNA mimic. miRNA internalisation and knockdown of a miR-19b-3p target gene, secretory leucoprotease inhibitor (SLPI), were determined by qRT-PCR. Results: Microparticle formulations were consistently found to be 2–3μm and all had a negative ζ potential (−5 mV to −14 mV). Encapsulation efficiency of premiR-19b-3p was 37.6 ± 13.4%. Levels of mature miR-19b-3p were higher in macrophages after delivery of premiR-19b-3p microparticles compared to empty or scrambled control miRNA-containing microparticles. Significant SLPI knockdown was achieved 72 hours post-delivery of premiR-19b-3p microparticles compared to controls. Conclusions: miRNA-encapsulating PLGA microparticles offer a new treatment paradigm for delivery to macrophages that could potentially be administered to CF lungs via inhalation. View Full-Text
Keywords: microRNA; microparticle; secretory leucoprotease inhibitor; macrophage microRNA; microparticle; secretory leucoprotease inhibitor; macrophage

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McKiernan, P.J.; Lynch, P.; Ramsey, J.M.; Cryan, S.A.; Greene, C.M. Knockdown of Gene Expression in Macrophages by microRNA Mimic-Containing Poly (Lactic-co-glycolic Acid) Microparticles. Medicines 2018, 5, 133.

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