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

1
Department of Medicine, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland
2
Drug Delivery and Advanced Materials Team, School of Pharmacy, Royal College of Surgeons in Ireland, Dublin 2, Ireland
3
Centre for Research in Medical Devices (CURAM), RCSI, Dublin and National University of Ireland, Galway H91 HE94, Ireland
4
Trinity Centre for Bioengineering, Trinity College Dublin, Dublin 2, Ireland
5
Tissue Engineering Research Group, Royal College of Surgeons in Ireland, 123 St Stephens Green, Dublin 2, Ireland
6
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; https://doi.org/10.3390/medicines5040133
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)
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Abstract

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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