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Pentablock copolymers of poly(ethylene glycol), poly((2-dimethyl amino)ethyl methacrylate) and poly(2-hydroxyethyl methacrylate) from consecutive atom transfer radical polymerizations for non-viral gene delivery

Paper ID Volume ID Publish Year Pages File Format Full-Text
11093 717 2008 11 PDF Available
Title
Pentablock copolymers of poly(ethylene glycol), poly((2-dimethyl amino)ethyl methacrylate) and poly(2-hydroxyethyl methacrylate) from consecutive atom transfer radical polymerizations for non-viral gene delivery
Abstract

Well-defined pentablock copolymers (PBPs) of P(HEMA)-b-P(DMAEMA)-b-PEG-b-P(DMAEMA)-b-P(HEMA) (in which PEG = poly(ethylene glycol), P(DMAEMA) = poly((2-dimethyl amino)ethyl methacrylate), and P(HEMA) = poly(2-hydroxyethyl methacrylate)), with different block lengths of P(DMAEMA), for non-viral gene delivery were prepared via consecutive atom transfer radical polymerizations (ATRPs) from the same di-2-bromoisobutyryl-terminated PEG (Br–PEG–Br) center block. The PBPs demonstrate good ability to condense plasmid DNA (pDNA) into 100–160 nm size nanoparticles with positive zeta potentials of 25–35 mV at PBPs/pDNA weight ratios of 5–25. The PBPs exhibit very low in vitro cytotoxicity and excellent gene transfection efficiency in HEK293 and COS7 cells. In particular, the transfection efficiencies of all the PBPs in HEK293 cells are comparable to, or higher than those of polyethylenimine (PEI, 25 kDa) at most weight ratios. The ability of the copolymers to condense plasmid DNA and the transfection efficiency of the resulting complexes are dependent on the chain length of P(DMAEMA) blocks. In addition to reducing the cytotoxicity and increasing the stability of the plasmid complexes, the PEG center block and the short P(HEMA) end blocks also help to enhance the gene transfection efficiency. Thus, the approach to well-defined block copolymers via ATRP provides a versatile means for tailoring the structure of non-viral gene vectors to meet the requirements of low cytotoxicity, good stability and high transfection capability for gene therapy applications.

Keywords
PEG; P(DMAEMA); P(HEMA); Pentablock copolymers; ATRP; Gene delivery
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Pentablock copolymers of poly(ethylene glycol), poly((2-dimethyl amino)ethyl methacrylate) and poly(2-hydroxyethyl methacrylate) from consecutive atom transfer radical polymerizations for non-viral gene delivery
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 29, Issue 20, July 2008, Pages 3023–3033
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