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Hydrophobic modification of low molecular weight polyethylenimine for improved gene transfection

Paper ID Volume ID Publish Year Pages File Format Full-Text
6388 488 2013 9 PDF Available
Title
Hydrophobic modification of low molecular weight polyethylenimine for improved gene transfection
Abstract

Hydrophobic modification of low molecular weight (LMW) polyethylenimine (PEI) is known to increase gene transfection efficiency of LMW PEI. However, few studies have explored how the conjugated hydrophobic groups influence the properties of the modified LMW PEI mainly due to difficulties in obtaining well defined final product compositions and limitations in current chemical synthesis routes. The aim of this study was to modify LMW PEI (Mn 1.8 kDa, PEI-1.8) judiciously with different hydrophobic functional groups and to investigate how hydrophobicity, molecular structure and inclusion of hydrogen bonding properties in the conjugated side groups as well as the conjugation degree (number of primary amine groups of PEI-1.8 modified with hydrophobic groups) influence PEI-1.8 gene transfection efficiency. The modified polymers were characterized for DNA binding ability, particle size, zeta potential, in vitro gene transfection efficiency and cytotoxicity in SKOV-3 human ovarian cancer and HepG2 human liver carcinoma cell lines. The study shows that modified PEI-1.8 polymers are able to condense plasmid DNA into cationic nanoparticles, of sizes ∼100 nm, whereas unmodified polymer/DNA complexes display larger particle sizes of 2 μm. Hydrophobic modification also increases the zeta potential of polymer/DNA complexes. Importantly, modified PEI-1.8 shows enhanced transfection efficiency over the unmodified counterpart. Higher transfection efficiency is obtained when PEI-1.8 is modified with shorter hydrophobic groups (MTC–ethyl) as opposed to longer ones (MTC–octyl and MTC–deodecyl). An aromatic structured functional group (MTC–benzyl) also enhances transfection efficiency more than an alkyl functional group (MTC–octyl). An added hydrogen-bonding urea group in the conjugated functional group (MTC–urea) does not enhance transfection efficiency over one without urea (MTC–benzyl). The study also demonstrates that modification degree greatly influences gene transfection, and ∼100% substitution of primary amine groups leads to significantly lower gene transfection efficiency. These findings provide insights to modification of PEI for development of effective and non-cytotoxic non-viral vectors.

Keywords
Low-molecular-weight polyethylenimine; Hydrophobic modification; Cyclic carbonate; Nucleophilic addition; Gene transfection; Structure–function relationship
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Hydrophobic modification of low molecular weight polyethylenimine for improved gene transfection
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 34, Issue 32, October 2013, Pages 7971–7979
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