학회 | 한국고분자학회 |
학술대회 | 2005년 가을 (10/13 ~ 10/14, 제주 ICC) |
권호 | 30권 2호 |
발표분야 | 고분자를 이용한 유전자 전달 |
제목 | A novel degradable branched poly(ester amine)s based on polycaprolactone and polyethylenimine as a gene carrier |
초록 | Gene therapy has become a promising strategy for the treatment of many inheritable or acquired diseases which are currently considered as incurable. Safety and good transfection efficiency are the important properties which as an ideal carrier should bear. Polyethylenimine (PEI) is a non degradable gene carrier with high transfection efficiency. However, PEI has high cytotoxicity, which depends on its molecular weight. In this study, to reduce the cytotoxicity, degradable branched poly(ester amine)s, were synthesized with high transfection efficiency, low cytotoxicity and degradability, as a new gene carrier. The copolymers were synthesized by reaction of low molecular weight PEI (1.8, 1.2 and 0.6kDa) with polycaprolactone diacrylate. Polycaprolactone diacrylate such as hydrophobic, biodegradable and semi-crystalline linear aliphatic polyester, was reacted with highly cationic PEI through Micheal addition mechanism by the similar method of Park et al.(1). The complex formation between copolymers and plasmid DNA (pDNA), was characterized by gel retardation assay, dynamic light scattering (DLS), and atomic force microscopy (AFM) to determine complex formation, particle size, and morphology respectively and the parameters that affects the DNA transfection efficiency were investigated. These polymers were analyzed for their cytotoxicity and transfection efficiency on cultured HeLa, human cervix epithelial carcinoma cells, HepG2 Human hepatoblastoma cell lines and MG63 human osteosarcoma cell lines. In gel retardation assay, plasmid DNA was completely retarded at 5:1 N/P (nitrogen of the polymer/phosphate of the DNA) ratio. In vitro transfection assay showed that the transfection efficiency of degradable poly(ester amine)s was comparable to that of PEI 25K and was dependant on the molecular weight of the PEI used to synthesize the respective copolymer. Cytotoxicity study showed that copolymer exhibited low cytotoxic effects on cells even at high polymer concentration as compared to PEI 25K. (1) Park et al., J. Controlled Rel.,105(2005)367-380. |
저자 | 로히다스, 김태희, 김유경, 조명행, 조종수 |
소속 | 서울대 |
키워드 | Polyethyleneimine; Biodegradable; Polycaprolactone; Gene delivery |