Galactosylated chitosan-g-PEI/DNA complexes-loaded poly(organophosphazene) hydrogel as a hepatocyte targeting gene delivery system.
Hydrogels are widely used in drug delivery systems because they can control the release and thereby enhance the efficiency of locally delivered bioactive molecules such as therapeutic drugs, proteins, or genes. For gene delivery, localized release of plasmid DNA or polymer/DNA complexes can transfect cells and produce sustained protein production. We tested the galactosylated chitosan-graft-polyethylenimine (GC-g-PEI)/DNA complexes-loaded poly(organophosphazene) thermosensitive biodegradable hydrogel as a hepatocyte targeting gene delivery system. The poly(organophosphazene) hydrogel loaded with GC-g-PEI/DNA complexes showed low cytotoxicity and higher transfection efficiency than PEI/DNA complexes, as well as good hepatocyte specificity in vitro and in vivo. Our results indicate that poly(organophosphazene) hydrogels loaded with GC-g-PEI/DNA complexes may be a safe and efficient hepatocyte targeting gene delivery system.
Jiang
Hu-Lin
HL
College of Veterinary Medicine, Seoul National University, Seoul, 151-742, Korea.
Kim
You-Kyoung
YK
Lee
Sun-Mi
SM
Park
Mi-Ran
MR
Kim
Eun-Mi
EM
Jin
Yong-Mei
YM
Arote
Rohidas
R
Jeong
Hwan-Jeong
HJ
Song
Soo-Chang
SC
Cho
Myung-Haing
MH
Cho
Chong-Su
CS
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D004247:DNA / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D005260:Female; D018014:Gene Transfer Techniques; D006367:HeLa Cells; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D020100:Hydrogels / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D009943:Organophosphorus Compounds / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D011094:Polyethyleneimine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D011108:Polymers / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D012995:Solubility; D014162:Transfection; D014783:Viscosity
D004337:Drug Carriers; D020100:Hydrogels; D009943:Organophosphorus Compounds; D011108:Polymers; C551320:chitosan-graft-polyethylenimine; C515246:poly(organophosphazene); D011094:Polyethyleneimine; D004247:DNA; D048271:Chitosan; C427203:calf thymus DNA