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Poly(aspartate-g-PEI800), a polyethylenimine analogue of low toxicity and high transfection efficiency for gene delivery

Paper ID Volume ID Publish Year Pages File Format Full-Text
10657 696 2007 12 PDF Available
Title
Poly(aspartate-g-PEI800), a polyethylenimine analogue of low toxicity and high transfection efficiency for gene delivery
Abstract

High-molecular-weight polyethylenimine (25 kDa, PEI25k) is one of the most common cationic polymers utilized in non-viral gene therapy. However, its methylene backbone (–CH2CH2Nx–) and high charge density can result in poor biodegradability and high toxicity to cells. We hypothesize that optimizing the polymer length and charge density of PEI analogues may result in decreased toxicity and higher transfection efficiency, and improved biocompatibility in vivo. A series of PEI analogues with controlled molecular weight and charge density were synthesized by grafting low-molecular-weight PEI800 (800 Da) to a polyaspartate peptide backbone of varying degrees of polymerization. The optimum polymer had a degree of polymerization of 65 with an average of 16 PEI800 groups conjugated to it. All of the polycations investigated in the study caused inflammation and apoptosis/necrosis in the liver and spleen of rodents 24 h post-injection; however, by day 5, the optimized poly(aspartate-g-PEI800) polymer and PEI800 did not show tissue damage or apoptosis, whereas PEI25k exhibited evidence of apoptosis/necrosis in the kidneys and spleen. Our study points to the need to optimize gene carriers to minimize toxicity, especially important for the safe delivery of therapeutic genes to explicit organs.

Keywords
Polyamino acid; Immunochemistry; Apoptosis; Cytotoxicity; Gene therapy
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Poly(aspartate-g-PEI800), a polyethylenimine analogue of low toxicity and high transfection efficiency for gene delivery
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 28, Issue 32, November 2007, Pages 4889–4900
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