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Galactosylated chitosan-graft-polyethylenimine as a gene carrier for hepatocyte targeting

Cited 111 time in Web of Science Cited 124 time in Scopus
Authors
Jiang, H-L; Kwon, J-T; Kim, Y-K; Kim, E-M; Arote, R.; Jeong, H-J; Nah, J-W; Choi, Y-J; Akaike, T.; Cho, Myung-Haing; Cho, C-S
Issue Date
2007-10
Publisher
Nature Publishing Group
Citation
Gene Therapy, Vol.14 No.19, pp.1389-1398
Keywords
nonviral vectortargeting gene deliverygalactosylated chitosan-graft-PEIintraperitoneal administration
Abstract
Chitosans have been proposed as alternative, biocompatible cationic polymers for nonviral gene delivery. However, the low transfection efficiency and low specificity of chitosan need to be addressed before clinical application. We prepared galactosylated chitosan-graft-polyethylenimine (GC-g-PEI) copolymer by an imine reaction between period-ate-oxidized GC and low-molecular-weight PEI. The molecular weight and composition were characterized using gel permeation chromatography column with multi-angle laser scattering and H-1 nuclear magnetic resonance, respectively. The copolymer was complexed with plasmid DNA in various copolymer/DNA (N/P) charge ratios, and the complexes were characterized. GC-g-PEI showed good DNA-binding ability and superior protection of DNA from nuclease attack and had low cytotoxicity compared to PEI 25K. GC-g-PEI/DNA complexes showed higher transfection efficiency than PEI 25K in both HepG2 and HeLa cell lines. Transfection efficiency into HepG2, which has asialoglycoprotein receptors, was higher than that into HeLa, which does not. GC-g-PEI/DNA complexes also transfected liver cells in vivo after intraperitoneal (i.p.) administration more effectively than PEI 25K. These results suggest that GC-g-PEI can be used in gene therapy to improve transfection efficiency and hepatocyte specificity in vitro and in vivo.
ISSN
0969-7128
Language
English
URI
https://hdl.handle.net/10371/8328
DOI
https://doi.org/10.1038/sj.gt.3302997
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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