Degradable copolymer based on amphiphilic N-octyl-N-quatenary chitosan and low-molecular weight polyethylenimine for gene delivery
Chengchu Liu,1,2,* Qing Zhu,1,* Wenhui Wu,1 Xiaolin Xu,1 Xiaoyu Wang,3 Shen Gao,3 Kehai Liu11Department of Biopharmaceutics, College of Food Science and Technology, Shanghai Ocean University, Shanghai, China; 2Shanghai Engineering Research Center of Aquatic-Product Processing and Preservation, Shang...
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Dove Medical Press
2012
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oai:doaj.org-article:72ebfc14951d41ce92568f70d2a78a422021-12-02T00:22:24ZDegradable copolymer based on amphiphilic N-octyl-N-quatenary chitosan and low-molecular weight polyethylenimine for gene delivery1176-91141178-2013https://doaj.org/article/72ebfc14951d41ce92568f70d2a78a422012-10-01T00:00:00Zhttp://www.dovepress.com/degradable-copolymer-based-on-amphiphilic-n-octyl-n-quatenary-chitosan-a11204https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Chengchu Liu,1,2,* Qing Zhu,1,* Wenhui Wu,1 Xiaolin Xu,1 Xiaoyu Wang,3 Shen Gao,3 Kehai Liu11Department of Biopharmaceutics, College of Food Science and Technology, Shanghai Ocean University, Shanghai, China; 2Shanghai Engineering Research Center of Aquatic-Product Processing and Preservation, Shanghai, China; 3Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai China*The first two authors contributed equally to this workBackground: Chitosan shows particularly high biocompatibility and fairly low cytotoxicity. However, chitosan is insoluble at physiological pH. Moreover, it lacks charge, so shows poor transfection. In order to develop a new type of gene vector with high transfection efficiency and low cytotoxicity, amphiphilic chitosan was synthesized and linked with low-molecular weight polyethylenimine (PEI).Methods: We first synthesized amphiphilic chitosan – N-octyl-N-quatenary chitosan (OTMCS), then prepared degradable PEI derivates by cross-linking low-molecular weight PEI with amphiphilic chitosan to produce a new polymeric gene vector (OTMCS–PEI). The new gene vector was characterized by various physicochemical methods. We also determined its cytotoxicity and gene transfecton efficiency in vitro and in vivo.Results: The vector showed controlled degradation. It was very stable and showed excellent buffering capacity. The particle sizes of the OTMCS–PEI/DNA complexes were around 150–200 nm with proper zeta potentials from 10 mV to 30 mV. The polymer could protect plasmid DNA from being digested by DNase I at a concentration of 2.25 U DNase I/µg DNA. Furthermore, they were resistant to dissociation induced by 50% fetal bovine serum and 1100 µg/mL sodium heparin. OTMCS–PEI revealed lower cytotoxicity, even at higher doses. Compared with PEI 25 KDa, the OTMCS–PEI/DNA complexes also showed higher transfection efficiency in vitro and in vivo.Conclusion: OTMCS–PEI was a potential candidate as a safe and efficient gene vector for gene therapy.Keywords: nonviral gene vector, polyethylenimine, transfection efficiency, cytotoxicityLiu CCZhu QWu WHXu XLWang XYGao SLiu KHDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 5339-5350 (2012) |
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Medicine (General) R5-920 |
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Medicine (General) R5-920 Liu CC Zhu Q Wu WH Xu XL Wang XY Gao S Liu KH Degradable copolymer based on amphiphilic N-octyl-N-quatenary chitosan and low-molecular weight polyethylenimine for gene delivery |
| description |
Chengchu Liu,1,2,* Qing Zhu,1,* Wenhui Wu,1 Xiaolin Xu,1 Xiaoyu Wang,3 Shen Gao,3 Kehai Liu11Department of Biopharmaceutics, College of Food Science and Technology, Shanghai Ocean University, Shanghai, China; 2Shanghai Engineering Research Center of Aquatic-Product Processing and Preservation, Shanghai, China; 3Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai China*The first two authors contributed equally to this workBackground: Chitosan shows particularly high biocompatibility and fairly low cytotoxicity. However, chitosan is insoluble at physiological pH. Moreover, it lacks charge, so shows poor transfection. In order to develop a new type of gene vector with high transfection efficiency and low cytotoxicity, amphiphilic chitosan was synthesized and linked with low-molecular weight polyethylenimine (PEI).Methods: We first synthesized amphiphilic chitosan – N-octyl-N-quatenary chitosan (OTMCS), then prepared degradable PEI derivates by cross-linking low-molecular weight PEI with amphiphilic chitosan to produce a new polymeric gene vector (OTMCS–PEI). The new gene vector was characterized by various physicochemical methods. We also determined its cytotoxicity and gene transfecton efficiency in vitro and in vivo.Results: The vector showed controlled degradation. It was very stable and showed excellent buffering capacity. The particle sizes of the OTMCS–PEI/DNA complexes were around 150–200 nm with proper zeta potentials from 10 mV to 30 mV. The polymer could protect plasmid DNA from being digested by DNase I at a concentration of 2.25 U DNase I/µg DNA. Furthermore, they were resistant to dissociation induced by 50% fetal bovine serum and 1100 µg/mL sodium heparin. OTMCS–PEI revealed lower cytotoxicity, even at higher doses. Compared with PEI 25 KDa, the OTMCS–PEI/DNA complexes also showed higher transfection efficiency in vitro and in vivo.Conclusion: OTMCS–PEI was a potential candidate as a safe and efficient gene vector for gene therapy.Keywords: nonviral gene vector, polyethylenimine, transfection efficiency, cytotoxicity |
| format |
article |
| author |
Liu CC Zhu Q Wu WH Xu XL Wang XY Gao S Liu KH |
| author_facet |
Liu CC Zhu Q Wu WH Xu XL Wang XY Gao S Liu KH |
| author_sort |
Liu CC |
| title |
Degradable copolymer based on amphiphilic N-octyl-N-quatenary chitosan and low-molecular weight polyethylenimine for gene delivery |
| title_short |
Degradable copolymer based on amphiphilic N-octyl-N-quatenary chitosan and low-molecular weight polyethylenimine for gene delivery |
| title_full |
Degradable copolymer based on amphiphilic N-octyl-N-quatenary chitosan and low-molecular weight polyethylenimine for gene delivery |
| title_fullStr |
Degradable copolymer based on amphiphilic N-octyl-N-quatenary chitosan and low-molecular weight polyethylenimine for gene delivery |
| title_full_unstemmed |
Degradable copolymer based on amphiphilic N-octyl-N-quatenary chitosan and low-molecular weight polyethylenimine for gene delivery |
| title_sort |
degradable copolymer based on amphiphilic n-octyl-n-quatenary chitosan and low-molecular weight polyethylenimine for gene delivery |
| publisher |
Dove Medical Press |
| publishDate |
2012 |
| url |
https://doaj.org/article/72ebfc14951d41ce92568f70d2a78a42 |
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