title: Galactose-poly(ethylene glycol)-polyethylenimine for improved lung gene transfer.
abstract: Polyethylenimine (PEI) is a potential gene transfer agent, but is limited by its poor transfection efficiency in vivo due to poor solubility and stability, pronounced toxicity and non-specific interaction with target cells. To improve its pulmonary gene transfection property, galactose (whose binding lectins are abundantly expressed in the lung) was selected as a ligand to improve the binding and uptake of the modified PEI/pDNA (plasmid DNA) polyplexes into lung cells. A novel protocol was developed to synthesize galactose-polyethylenglycol (PEG)-PEI copolymers. The resulting galactose-PEG-PEI/pDNA polyplexes showed improved solubility, stability, and reduced toxicity. Compared with that obtained by PEI/pDNA at a N/P ratio of 6, the transfection efficiency of 1% galactose-PEG-PEI/pDNA polyplexes at the N/P ratio of 36 was 4.5- and 11.6-fold in the A549 cell line and in mice lung, respectively. These data taken suggest that galactose-PEG-PEI may be a promising pulmonary gene delivery system.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, 138 Yixueyuan Road, Shanghai 200032, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Gao
authors.forename: Kaili
authors.initials: K
authors.lastname: Hu
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Pang
authors.forename: Jia
authors.initials: J
authors.lastname: Cai
authors.forename: Jingwei
authors.initials: J
authors.lastname: Li
authors.forename: Hongbing
authors.initials: H
authors.lastname: Wu
authors.forename: Xinguo
authors.initials: X
authors.lastname: Jiang
mesh_terms: D000588:Amines / Q000737:chemistry; D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D004247:DNA / Q000737:chemistry*; D015316:Genetic Therapy; D005822:Genetic Vectors; D008168:Lung; D051379:Mice; D010957:Plasmids / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000633:toxicity; D011094:Polyethyleneimine / Q000737:chemistry* / Q000633:toxicity; D012995:Solubility; D014162:Transfection
chemical_list: D000588:Amines; C531908:galactose-poly(ethylene glycol)-polyethylenimine; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D004247:DNA