Glial cell line-derived neurotrophic factor gene delivery via a polyethylene imine grafted chitosan carrier

Yu-Shiang Peng,1,* Po-Liang Lai,2,* Sydney Peng,1 His-Chin Wu,3 Siang Yu,1 Tsan-Yun Tseng,4 Li-Fang Wang,5 I-Ming Chu1 1Department of Chemical Engineering, National Tsing Hua University, Hsinchu, 2Department of Orthopedic Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University Colle...

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Autores principales:	Peng YS, Lai PL, Peng S, Wu HC, Yu S, Tseng TY, Wang LF, Chu IM
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/ae7313f292db49518976fe43f3b716da
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spelling	oai:doaj.org-article:ae7313f292db49518976fe43f3b716da2021-12-02T05:10:44ZGlial cell line-derived neurotrophic factor gene delivery via a polyethylene imine grafted chitosan carrier1178-2013https://doaj.org/article/ae7313f292db49518976fe43f3b716da2014-06-01T00:00:00Zhttp://www.dovepress.com/glial-cell-line-derived-neurotrophic-factor-gene-delivery-via-a-polyet-a17408https://doaj.org/toc/1178-2013 Yu-Shiang Peng,1,* Po-Liang Lai,2,* Sydney Peng,1 His-Chin Wu,3 Siang Yu,1 Tsan-Yun Tseng,4 Li-Fang Wang,5 I-Ming Chu1 1Department of Chemical Engineering, National Tsing Hua University, Hsinchu, 2Department of Orthopedic Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, 3Department of Materials Engineering, Tatung University, Taipei, 4Graduate School of Biotechnology and Bioengineering, College of Engineering, Yuan Ze University, Chung-Li, 5Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, Taiwan *Yu-Shiang Peng and Po-Liang Lai contributed equally to this work 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. Keywords: chitosan, gene transfection, glial cell, Parkinson’s disease, polyethylene iminePeng YSLai PLPeng SWu HCYu STseng TYWang LFChu IMDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 3163-3174 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Peng YS Lai PL Peng S Wu HC Yu S Tseng TY Wang LF Chu IM Glial cell line-derived neurotrophic factor gene delivery via a polyethylene imine grafted chitosan carrier
description	Yu-Shiang Peng,1,* Po-Liang Lai,2,* Sydney Peng,1 His-Chin Wu,3 Siang Yu,1 Tsan-Yun Tseng,4 Li-Fang Wang,5 I-Ming Chu1 1Department of Chemical Engineering, National Tsing Hua University, Hsinchu, 2Department of Orthopedic Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, 3Department of Materials Engineering, Tatung University, Taipei, 4Graduate School of Biotechnology and Bioengineering, College of Engineering, Yuan Ze University, Chung-Li, 5Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, Taiwan *Yu-Shiang Peng and Po-Liang Lai contributed equally to this work 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. Keywords: chitosan, gene transfection, glial cell, Parkinson’s disease, polyethylene imine
format	article
author	Peng YS Lai PL Peng S Wu HC Yu S Tseng TY Wang LF Chu IM
author_facet	Peng YS Lai PL Peng S Wu HC Yu S Tseng TY Wang LF Chu IM
author_sort	Peng YS
title	Glial cell line-derived neurotrophic factor gene delivery via a polyethylene imine grafted chitosan carrier
title_short	Glial cell line-derived neurotrophic factor gene delivery via a polyethylene imine grafted chitosan carrier
title_full	Glial cell line-derived neurotrophic factor gene delivery via a polyethylene imine grafted chitosan carrier
title_fullStr	Glial cell line-derived neurotrophic factor gene delivery via a polyethylene imine grafted chitosan carrier
title_full_unstemmed	Glial cell line-derived neurotrophic factor gene delivery via a polyethylene imine grafted chitosan carrier
title_sort	glial cell line-derived neurotrophic factor gene delivery via a polyethylene imine grafted chitosan carrier
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/ae7313f292db49518976fe43f3b716da
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Glial cell line-derived neurotrophic factor gene delivery via a polyethylene imine grafted chitosan carrier

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