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Degradable polyethylenimine-alt-poly(ethylene glycol) copolymers as novel gene carriers

Cited 207 time in Web of Science Cited 151 time in Scopus
Authors
Park, Mi Ran; Han, Ki Ok; Han, In Kwon; Cho, Myung Haing; Nah, Jae Woon; Choi, Yun Jaie; Cho, Chong Su
Issue Date
2005-07
Citation
Journal of Controlled Release, Vol.105 No.3, pp.367-380
Keywords
polyethyleniminedegradablegene deliverypoly(ethylene glycol)
Abstract
An ideal gene carrier requires both safety and transfection efficiency. Polyethylenimine (PEI) is a well-known cationic polymer, which has high transfection efficiency owing to its buffering capacity. But it has been reported that PEI is cytotoxic in many cell lines and non-degradable. In this study, we synthesized degradable PEI-alt-poly(ethylene glycol) (PEG) copolymers using Michael-type addition reactions as a new gene carrier and characterized them. These copolymers were complexed with plasmid DNA and the resulting complexes were characterized by dynamic light scattering, gel retardation and atomic force microscopy to determine particle sizes, complex formation and complex shape, respectively. Cytotoxicity and transfection efficiency of the copolymers were also checked in cultured HeLa human cervix epithelial carcinoma cells, HepG2 human hepatoblastoma cell line and MG63 human osteosarcoma cells. PEG to PEI ratio in the copolymers was near I and the molecular weight of the copolymer ranged from around 8000 to 12,900. These copolymers degraded rapidly at 37 degrees C in 0.1 M phosphate buffered saline (PBS, pH 7.4). The complete copolymer/DNA complex was formed at an N/P ratio of 12, producing a complex resistant to DNase I. Particle sizes decreased with increasing N/P ratio and PEG molecular weight, exhibiting a minimum value of 75 nm at an N/P ratio of 45 with PEI-alt-PEG (700). Cytotoxicity study showed that copolymers exhibited no cytotoxic effects on cells even at high copolymer concentration. Also, transfection efficiency was influenced by PEG molecular weight and, in case of PEI-alt-PEG (258), the transfection efficiency was higher than that for PEI 25 K in HepG2 and MG63, whereas it was lower than that for PEI 25K in HeLa cells. (c) 2005 Elsevier B.V. All rights reserved.
ISSN
0168-3659
URI
https://hdl.handle.net/10371/172427
DOI
https://doi.org/10.1016/j.jconrel.2005.04.008
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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