학회 | 한국고분자학회 |
학술대회 | 2004년 가을 (10/08 ~ 10/09, 경북대학교) |
권호 | 29권 2호, p.647 |
발표분야 | 의료용 고분자 부문위원회 |
제목 | Degradable Polyethylenimine-alt-Poly(ethylene glycol) Copolymers as a Novel Gene Carrier |
초록 | An ideal gene carrier requires both safety and transfection effciency. Polyethylenimine (PEI) is a well-known cationic polymer which has high transfection efficiency owing to its buffering capacity1-2. But it has been reported that the 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 reaction as a new gene carrier and characterized. The copolymers were complexed with plasmid DNA and the resulting complexes were characterized by dynamic light scattering, gel retardation and atomic force microscopy to determine the particle sizes, complex formation and shape of complex, 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. The composition of PEG to PEI in the copolymers was around 1 and the molecular weight of the copolymer was from around 8000 to 12900. The copolymers degraded rapidly under physiological condition. The complete copolymer/DNA complex was formed at the charge ratio of 12 and the complex to DNaseⅠ resistance was obtained. The particle sizes decreased with an increase of charge ratio of copolymer to DNA, molecular weight of PEG and had a minimum value around 75nm at the charge ratio of 45 in the PEI-alt-PEG(700). And the complex was observed as spherical shapes. Cytotoxicity study showed that the copolymer had no cytotoxic effects on cells even at high concentration of copolymers. Also, transfection efficiency was dependent on cell type and was higher than that of PEI 25K into HepG2 and MG63 whereas the transfection efficiency into HeLa was lower than that of PEI 25K. References (1) O. Boussif, F. Lezoualc'h, M.A. Zanta, M.D. Mergny, D. Scherman, B. Demeneix, and J.P. Behr, Proc. Natl. Acad. Sci. USA, 92, 7297 (1995). (2) W. T. Godbey, K. K. Wu, and A. G. Mikos, J. controlled Release, 60, 149 (1999). |
저자 | 박미란1, 한기옥2, 조명행1, 나재운3, 조종수1 |
소속 | 1서울대, 2성균관대, 3순천대 |
키워드 | Polyethylenimine; Degradable; Gene delivery; Poly(ethylene glycol) |