title: Glial cell line-derived neurotrophic factor gene delivery via a polyethylene imine grafted chitosan carrier.
abstract: Parkinson's disease is known to result from the loss of dopaminergic neurons. Direct intracerebral injections of high doses of recombinant glial cell line-derived neurotrophic factor (GDNF) have been shown to protect adult nigral dopaminergic neurons. Because GDNF does not cross the blood-brain barrier, intracerebral gene transfer is an ideal option. Chitosan (CHI) is a naturally derived material that has been used for gene transfer. However, the low water solubility often leads to decreased transfection efficiency. Grafting of highly water-soluble polyethylene imines (PEI) and polyethylene glycol onto polymers can increase their solubility. The purpose of this study was to design a non-viral gene carrier with improved water solubility as well as enhanced transfection efficiency for treating Parkinsonism. Two molecular weights (Mw =600 and 1,800 g/mol) of PEI were grafted onto CHI (PEI600-g-CHI and PEI1800-g-CHI, respectively) by opening the epoxide ring of ethylene glycol diglycidyl ether (EX-810). This modification resulted in a non-viral gene carrier with less cytotoxicity. The transfection efficiency of PEI600-g-CHI/deoxyribonucleic acid (DNA) polyplexes was significantly higher than either PEI1800-g-CHI/DNA or CHI/DNA polyplexes. The maximal GDNF expression of PEI600-g-CHI/DNA was at the polymer:DNA weight ratio of 10:1, which was 1.7-fold higher than the maximal GDNF expression of PEI1800-g-CHI/DNA. The low toxicity and high transfection efficiency of PEI600-g-CHI make it ideal for application to GDNF gene therapy, which has potential for the treatment of Parkinson's disease.
authors: Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan.
authors: Yu-Shiang
authors: YS
authors: Peng
authors: Department of Orthopedic Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors: Po-Liang
authors: PL
authors: Lai
authors: Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan.
authors: Sydney
authors: S
authors: Peng
authors: Department of Materials Engineering, Tatung University, Taipei, Taiwan.
authors: His-Chin
authors: HC
authors: Wu
authors: Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan.
authors: Siang
authors: S
authors: Yu
authors: Graduate School of Biotechnology and Bioengineering, College of Engineering, Yuan Ze University, Chung-Li, Taiwan.
authors: Tsan-Yun
authors: TY
authors: Tseng
authors: Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Li-Fang
authors: LF
authors: Wang
authors: Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan.
authors: I-Ming
authors: IM
authors: Chu
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D004247:DNA / Q000235:genetics* / Q000378:metabolism / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D011094:Polyethyleneimine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D012995:Solubility; D014162:Transfection / Q000379:methods*
chemical_list: D004337:Drug Carriers; D051100:Glial Cell Line-Derived Neurotrophic Factor; C551320:chitosan-graft-polyethylenimine; D011094:Polyethyleneimine; D004247:DNA; D048271:Chitosan
keywords: Parkinson’s disease; chitosan; gene transfection; glial cell; polyethylene imine