title: Heparin-conjugated polyethylenimine for gene delivery.
abstract: A major problem when using cationic polymers for gene delivery is that transfection is strongly inhibited by the presence of serum. This shortcoming limits the application of cationic polymers for systematic gene delivery in vivo. Due to the shielding effect of heparin, heparin conjugation to cationic polymers may improve the in vivo gene transfection efficiency. In this study, the transfection efficiency of heparin-conjugated polyethylenimine (HCPEI) with a low molecular weight of 1800 Da was compared to the transfection efficiencies of polyethylenimine with a low molecular weight of 1800 Da (PEI1800), polyethylenimine with a high molecular weight of 25,000 Da (PEI25k), and Lipofectamine. The size of the HCPEI/plasmid DNA (pDNA) complex is approximately 250 nm. HCPEI has a proton-buffering effect and HCPEI/pDNA has higher blood compatibility and a lower cytotoxicity than PEI25k/pDNA and Lipofectamine/pDNA. For in vitro transfection of rabbit smooth muscle cells in serum-free medium, the transfection efficiency of HCPEI/pDNA was not significantly different from those of PEI25k/pDNA and Lipofectamine/pDNA. Importantly, in serum-containing medium, the transfection efficiency of HCPEI/pDNA was significantly higher than those of PEI25k/pDNA and Lipofectamine/pDNA. For vascular endothelial growth factor (VEGF) gene transfection to mouse ischemic limbs, HCPEI/pDNA exhibited significantly higher VEGF expression and more extensive neovascularization than PEI/pDNA and Lipofectamine/pDNA. Taken together, heparin conjugation to PEI improves the in vivo gene transfection efficiency of PEI.
authors.affiliation: Department of Chemical Engineering, Hanyang University, 17 Haengdang-dong, Seongdong-gu, Seoul 133-791, Republic of Korea.
authors.forename: Oju
authors.initials: O
authors.lastname: Jeon
authors.forename: Hee Seok
authors.initials: HS
authors.lastname: Yang
authors.forename: Tae-Jin
authors.initials: TJ
authors.lastname: Lee
authors.forename: Byung-Soo
authors.initials: BS
authors.lastname: Kim
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004195:Disease Models, Animal; D004903:Erythrocyte Aggregation / Q000187:drug effects; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006493:Heparin / Q000737:chemistry* / Q000633:toxicity; D006614:Hindlimb; D007511:Ischemia / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D008055:Lipids / Q000737:chemistry* / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D018482:Muscle, Skeletal / Q000098:blood supply; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D018919:Neovascularization, Physiologic; D010316:Particle Size; D011094:Polyethyleneimine / Q000737:chemistry* / Q000633:toxicity; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection / Q000379:methods*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D008055:Lipids; C086724:Lipofectamine; D042461:Vascular Endothelial Growth Factor A; D011094:Polyethyleneimine; D006493:Heparin; D004247:DNA