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Non-ionic amphiphilic biodegradable PEG-PLGA-PEG copolymer enhances gene delivery efficiency in rat skeletal muscle

Authors
 Chien-Wen Chang  ;  Donghoon Choi  ;  Sung Wan Kim  ;  Yong-Hee Kim  ;  Lane V. Christensen  ;  James W. Yockman  ;  Won Jong Kim 
Citation
 JOURNAL OF CONTROLLED RELEASE, Vol.118(2) : 245-253, 2007 
Journal Title
 JOURNAL OF CONTROLLED RELEASE 
ISSN
 0168-3659 
Issue Date
2007
MeSH
Animals ; Cell Line ; Cell Survival/drug effects ; Electrophoresis, Agar Gel ; Genes, Reporter ; Humans ; Luciferases ; Male ; Mice ; Microscopy, Atomic Force ; Muscle, Skeletal/drug effects ; Muscle, Skeletal/metabolism* ; Nucleic Acid Conformation ; Plasmids/chemistry ; Plasmids/metabolism* ; Poloxalene/toxicity ; Polyethylene Glycols/chemistry* ; Polyethylene Glycols/toxicity ; Polyethyleneimine/chemistry ; Polyglactin 910/chemistry* ; Polyglactin 910/toxicity ; Rats ; Rats, Sprague-Dawley ; Surface Properties ; Time Factors ; Transfection/methods* ; Vascular Endothelial Growth Factor A/biosynthesis ; Vascular Endothelial Growth Factor A/genetics
Keywords
Gene therapy ; PEG–PLGA–PEG ; Skeletal muscle ; Plasmid DNA ; VEGF ; Biodegradable
Abstract
Naked plasmid DNA (pDNA)-based gene therapy has low delivery efficiency, and consequently, low therapeutic effect. We present a biodegradable nonionic triblock copolymer, PEG13–PLGA10–PEG13, to enhance gene delivery efficiency in skeletal muscle. Effects of PEG13–PLGA10–PEG13 on physicochemical properties of pDNA were evaluated by atomic force microscopy (AFM) imaging, gel electrophoresis and zeta-potential analysis. AFM imaging suggested a slightly compacted structure of pDNA when it was mixed with the polymer, while zeta-potential measurement indicated an increased surface potential of negatively charged pDNA. PEG13–PLGA10–PEG13 showed a relatively lower toxicity compared to Pluronic P85 in a skeletal muscle cell line. The luciferase expression of pDNA delivered in 0.25% polymer solution was up to three orders of magnitude more than branched polyethylenimine (bPEI(25 k))/pDNA and three times more than that of naked pDNA five days after intramuscular administration. This in vivo gene delivery enhancement was also observed displaying a two-fold higher expression of human vascular endothelial growth factor (VEGF). Based on fluorescence labeled pDNA distribution, it is speculated that the greater diffusivity of PEG13–PLGA10–PEG13/pDNA compared to bPEI(25 k)/pDNA accounts for better transfection efficiency in vivo. To summarize, combining PEG13–PLGA10–PEG13 with pDNA possesses the potential to improve gene delivery efficiency in skeletal muscle.
Full Text
http://www.sciencedirect.com/science/article/pii/S0168365906006791
DOI
10.1016/j.jconrel.2006.11.025
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Choi, Dong Hoon(최동훈) ORCID logo https://orcid.org/0000-0002-2009-9760
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/96287
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