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Enhancing in vivo circulation and siRNA delivery with biodegradable polyethylenimine-graft-polycaprolactone-block-poly(ethylene glycol) copolymers

Paper ID Volume ID Publish Year Pages File Format Full-Text
6581 501 2012 8 PDF Available
Title
Enhancing in vivo circulation and siRNA delivery with biodegradable polyethylenimine-graft-polycaprolactone-block-poly(ethylene glycol) copolymers
Abstract

The purpose of this study was to enhance the in vivo blood circulation time and siRNA delivery efficiency of biodegradable copolymers polyethylenimine-graft-polycaprolactone-block-poly(ethylene glycol) (hy-PEI-g-PCL-b-PEG) by introducing high graft densities of PCL-PEG chains. SYBR® Gold and heparin assays indicated improved stability of siRNA/copolymer-complexes with a graft density of 5. At N/P 1, only 40% siRNA condensation was achieved with non-grafted polymer, but 95% siRNA was condensed with copolymer PEI25k-(PCL570-PEG5k)5. Intracellular uptake studies with confocal laser scanning microscopy and flow cytometry showed that the cellular uptake was increased with graft density, and copolymer PEI25k-(PCL570-PEG5k)5 was able to deliver siRNA much more efficiently into the cytosol than into the nucleus. The in vitro knockdown effect of siRNA/hyPEI-g-PCL-b-PEG was also significantly improved with increasing graft density, and the most potent copolymer PEI25k-(PCL570-PEG5k)5 knocked down 84.43% of the GAPDH expression. Complexes of both the copolymers with graft density 3 and 5 circulated much longer than unmodified PEI25 kDa and free siRNA, leading to a longer elimination half-life, a slower clearance and a three- or fourfold increase of the AUC compared to free siRNA, respectively. We demonstrated that the graft density of the amphiphilic chains can enhance the siRNA delivery efficiency and blood circulation, which highlights the development of safe and efficient non-viral polymeric siRNA nanocarriers that are especially stable and provide longer circulation in vivo.

Keywords
siRNA delivery; Biodegradable polycations; Non-viral polymeric nanocarriers; In vivo biodistribution and pharmacokinetics; SPECT imaging
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Enhancing in vivo circulation and siRNA delivery with biodegradable polyethylenimine-graft-polycaprolactone-block-poly(ethylene glycol) copolymers
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 33, Issue 27, September 2012, Pages 6551–6558
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