Galactose-poly(ethylene glycol)-polyethylenimine for improved lung gene transfer |
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Authors: | Chen Jun Gao Xiaoling Hu Kaili Pang Zhiqing Cai Jia Li Jingwei Wu Hongbing Jiang Xinguo |
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Institution: | a Department of Pharmaceutics, School of Pharmacy, Fudan University, 138 Yixueyuan Road, Shanghai 200032, PR China b Department of Pharmacology, Institute of Medical Science, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China |
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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. |
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Keywords: | Non-viral gene therapy Galactose Poly(ethylene glycol) Polyethylenimine Lung |
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