Galactosylated poly(ethylene glycol)-chitosan-graft-polyethylenimine as a gene carrier for hepatocyte-targeting.
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.
Jiang
Hu-Lin
HL
Department of Agricultural Biotechnology, Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, South Korea.
Kwon
Jung-Taek
JT
Kim
Eun-Mi
EM
Kim
You-Kyoung
YK
Arote
Rohidas
R
Jere
Dhananjay
D
Jeong
Hwan-Jeong
HJ
Jang
Mi-Kyeong
MK
Nah
Jae-Woon
JW
Xu
Cheng-Xiong
CX
Park
In-Kyu
IK
Cho
Myung-Haing
MH
Cho
Chong-Su
CS
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
D001672:Biocompatible Materials; D004337:Drug Carriers; C534328:galactosylated poly(ethylene glycol)-chitosan-graft-polyethylenimine; D011094:Polyethyleneimine; D004247:DNA; D048271:Chitosan