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Glial cell line-derived neurotrophic factor gene delivery via a polyethylene imine grafted chitosan carrier
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 barr...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Dove Medical Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4085318/ https://www.ncbi.nlm.nih.gov/pubmed/25061293 http://dx.doi.org/10.2147/IJN.S60465 |
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author | Peng, Yu-Shiang Lai, Po-Liang Peng, Sydney Wu, His-Chin Yu, Siang Tseng, Tsan-Yun Wang, Li-Fang Chu, I-Ming |
author_facet | Peng, Yu-Shiang Lai, Po-Liang Peng, Sydney Wu, His-Chin Yu, Siang Tseng, Tsan-Yun Wang, Li-Fang Chu, I-Ming |
author_sort | Peng, Yu-Shiang |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4085318 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-40853182014-07-24 Glial cell line-derived neurotrophic factor gene delivery via a polyethylene imine grafted chitosan carrier Peng, Yu-Shiang Lai, Po-Liang Peng, Sydney Wu, His-Chin Yu, Siang Tseng, Tsan-Yun Wang, Li-Fang Chu, I-Ming Int J Nanomedicine Original Research 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. Dove Medical Press 2014-06-28 /pmc/articles/PMC4085318/ /pubmed/25061293 http://dx.doi.org/10.2147/IJN.S60465 Text en © 2014 Peng et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Peng, Yu-Shiang Lai, Po-Liang Peng, Sydney Wu, His-Chin Yu, Siang Tseng, Tsan-Yun Wang, Li-Fang Chu, I-Ming Glial cell line-derived neurotrophic factor gene delivery via a polyethylene imine grafted chitosan carrier |
title | 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_short | 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 |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4085318/ https://www.ncbi.nlm.nih.gov/pubmed/25061293 http://dx.doi.org/10.2147/IJN.S60465 |
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