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Transfection of macrophages by collagen hollow spheres loaded with polyplexes: A step towards modulating inflammation ☆

Paper ID Volume ID Publish Year Pages File Format Full-Text
334 38 2012 7 PDF Available
Title
Transfection of macrophages by collagen hollow spheres loaded with polyplexes: A step towards modulating inflammation ☆
Abstract

Macrophages are key orchestrators of inflammation as they secrete proteases and inflammatory cytokines. To date, therapies aimed at modulating macrophage phenotype have failed due to the short half-life of biomolecules in the body. Therefore, inhibition of inflammation by gene therapy constitutes a new hope.In the present study, we have assessed collagen hollow spheres as a reservoir system for polyplexes in order to transfect human macrophages while preserving cell viability. Polyplexes were formed by complexing G-Luc plasmid with a poly(2-dimethylaminoethyl methacrylate) poly(ethylene glycol) based hyperbranched polymer. Several ratios of polymer/pDNA (5:1, 8:1, 10:1 w/w) complexes in two different sphere sizes (1.24 and 4.5 μm) were tested. Collagen hollow spheres were loaded with polyplexes up to 80 μg of pDNA per mg of microspheres. The release of polyplexes from the spheres was delayed and prolonged i.e. 20% of the initial amount released in 5 days. Following incubation with polyplex-loaded microspheres, macrophages were transfected (polyplex pDNA:polymer ratio 1:10 w/w). In addition, collagen hollow spheres maintained cell viability as more than 80% of cells were viable after 4 days in culture. In contrast, when used alone, polyplexes were seen to be toxic, while there was no transfection detected. Taken together, these results show that collagen hollow spheres may be used as a reservoir for controlled gene delivery to macrophages. Unlike existing gene delivery systems, this system allows for macrophage transfection with minimal toxicity. Hence, this system has a potential for the delivery of a therapeutic gene in order to modulate inflammation.

Keywords
Chronic inflammation; Macrophages; Collagen microspheres; Polyplexes; Gene delivery
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Transfection of macrophages by collagen hollow spheres loaded with polyplexes: A step towards modulating inflammation ☆
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Publisher
Database: Elsevier - ScienceDirect
Journal: Acta Biomaterialia - Volume 8, Issue 12, December 2012, Pages 4208–4214
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us