title: Galactosylated poly(ethylene glycol)-chitosan-graft-polyethylenimine as a gene carrier for hepatocyte-targeting.
abstract: Chitosan and chitosan derivatives have been proposed as alternative and biocompatible cationic polymers for non-viral gene delivery. However, the low transfection efficiency and low specificity of chitosan is an aspect of this approach that must be addressed prior to any clinical applications. In the present study a chitosan derivative, galactosylated poly(ethylene glycol)-chitosan-graft-polyethylenimine (Gal-PEG-CHI-g-PEI), was investigated as a potential hepatocyte-targeting gene carrier. The composition of Gal-PEG-CHI-g-PEI was characterized using (1)H nuclear magnetic resonance ((1)H NMR), and the particle size and zeta potential of Gal-PEG-CHI-g-PEI/DNA complexes were measured using dynamic light scattering (DLS). The Gal-PEG-CHI-g-PEI exhibited lower cytotoxicity compared to PEI 25K as a control. Likewise, Gal-PEG-CHI-g-PEI/DNA complexes showed good hepatocyte specificity. Furthermore, Gal-PEG-CHI-g-PEI/DNA complexes transfected liver cells more effectively than PEI 25K in vivo after intravenous (i.v.) administration. Together, these results suggest that Gal-PEG-CHI-g-PEI, which has improved transfection efficiency and hepatocyte specificity both in vitro and in vivo, may be useful for gene therapy.
authors.affiliation: Department of Agricultural Biotechnology, Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, South Korea.
authors.forename: Hu-Lin
authors.initials: HL
authors.lastname: Jiang
authors.forename: Jung-Taek
authors.initials: JT
authors.lastname: Kwon
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Kim
authors.forename: You-Kyoung
authors.initials: YK
authors.lastname: Kim
authors.forename: Rohidas
authors.initials: R
authors.lastname: Arote
authors.forename: Dhananjay
authors.initials: D
authors.lastname: Jere
authors.forename: Hwan-Jeong
authors.initials: HJ
authors.lastname: Jeong
authors.forename: Mi-Kyeong
authors.initials: MK
authors.lastname: Jang
authors.forename: Jae-Woon
authors.initials: JW
authors.lastname: Nah
authors.forename: Cheng-Xiong
authors.initials: CX
authors.lastname: Xu
authors.forename: In-Kyu
authors.initials: IK
authors.lastname: Park
authors.forename: Myung-Haing
authors.initials: MH
authors.lastname: Cho
authors.forename: Chong-Su
authors.initials: CS
authors.lastname: Cho
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000009:adverse effects / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D004337:Drug Carriers / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry; D005260:Female; D018014:Gene Transfer Techniques; D006367:HeLa Cells; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008807:Mice, Inbred BALB C; D010316:Particle Size; D011094:Polyethyleneimine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D014162:Transfection
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; C534328:galactosylated poly(ethylene glycol)-chitosan-graft-polyethylenimine; D011094:Polyethyleneimine; D004247:DNA; D048271:Chitosan