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Specific effects of PEGylation on gene delivery efficacy of polyethylenimine: Interplay between PEG substitution and N/P ratio

Paper ID Volume ID Publish Year Pages File Format Full-Text
371 40 2012 15 PDF Available
Title
Specific effects of PEGylation on gene delivery efficacy of polyethylenimine: Interplay between PEG substitution and N/P ratio
Abstract

While an effective non-viral gene carrier, 25 kDa branched polyethylenimine (PEI) is cytotoxic, and decreasing its toxicity while maintaining its functionality is vital. Conjugation of carriers with polyethylene glycol (PEG) is a common approach to decreasing toxicity and improving biodistribution; however, the effect of PEGylation on PEI transfection efficacy is contradictory at present. The aim of this work was to reveal the details of this dependence. Polymers were synthesized by grafting 2 kDa PEG to 25 kDa PEI at multiple ratios. Unlike typical investigations, parallel studies based on either total polymer weight or PEI-backbone weight were employed at the same time for accurate investigation into the specific effects of PEGylation. Polymers were assessed for toxicity and plasmid DNA (pDNA) binding, while polyplexes were formed at various polymer/pDNA weight ratios and monitored by dynamic light scattering (DLS) in the presence of serum. The efficacy of the polyplexes for pDNA delivery and transgene expression in HEK293 cells was assessed by flow cytometry. This approach unexpectedly revealed that increased PEG substitution caused lower toxicity and pDNA-binding on a per total polymer weight basis, but not on a per PEI-backbone weight basis. DLS indicated that high PEGylation prevents an increase in polyplex size in the presence of serum. Plasmid uptake and transgene expression were found to have a complex relationship with PEG substitution, dependent on the polymer/plasmid-DNA weight ratio. PEGylation generally decreased the transfection efficacy of PEI, but under ideal conditions of PEG substitution and polymer/pDNA ratio, PEGylation provided more effective carrier formulations than the native PEI itself.

Keywords
Gene delivery; Polymers; Nanocarriers; Polyethylene glycol; Polyethylenimine
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Specific effects of PEGylation on gene delivery efficacy of polyethylenimine: Interplay between PEG substitution and N/P ratio
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Publisher
Database: Elsevier - ScienceDirect
Journal: Acta Biomaterialia - Volume 8, Issue 11, November 2012, Pages 3941–3955
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