| 학회 | 한국고분자학회 |
| 학술대회 | 2005년 봄 (04/14 ~ 04/15, 전경련회관) |
| 권호 | 30권 1호, p.261 |
| 발표분야 | 의료용 고분자 부문위원회 |
| 제목 | Degradable Polyethylenimine-alt-Poly(ethylene glycol) Copolymer as a Novel Gene Carrier in vitro and in vivo |
| 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 capacity. 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 new gene carriers and characterized them. 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. Finally, biodistribution of gene expression after administration of copolymer/DNA complexes to mice was confirmed by aerosol and intravenous administrations. 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 at 37℃ in 0.1M phosphate buffered saline (PBS; pH 7.4). The complete copolymer/DNA complex was formed at the N/P ratio of 12 and the complex to DNaseⅠ resistance was obtained. The particle sizes decreased with an increase of N/P ratio, molecular weight of PEG and had a minimum value around 75nm at the N/P ratio of 45 in the PEI-alt-PEG(700). Cytotoxicity study showed that the copolymers had no cytotoxic property on cells even at high concentration of copolymers. Also, transfection efficiency was influenced by molecular weight of PEG, and in case of PEI-alt-PEG(258), the transfection efficiency was higher than that of PEI 25K in HepG2 and MG63 whereas it was lower than that of PEI 25K in HeLa. Furthermore, in vivo transfection, PEI-alt-PEG(258) mediated gene expression 10- to 100-fold more efficient in lung and liver than PEI 25K in both of intravenous and aerosol administrations. |
| 저자 | 박미란1, 한기옥2, 조명행1, 송수창3, 조종수1 |
| 소속 | 1서울대, 2성균관대, 3KIST 생체과학연구부 |
| 키워드 | Polyethylenimine; Poly(ethylene glycol); degradable polymer; gene delivery |
