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Degradable copolymer based on amphiphilic N-octyl-N-quatenary chitosan and low-molecular weight polyethylenimine for gene delivery

Authors Liu CC, Zhu Q, Wu WH, Xu XL, Wang XY, Gao S, Liu KH

Received 20 July 2012

Accepted for publication 22 August 2012

Published 8 October 2012 Volume 2012:7 Pages 5339—5350

DOI https://doi.org/10.2147/IJN.S36179

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Chengchu Liu,1,2,* Qing Zhu,1,* Wenhui Wu,1 Xiaolin Xu,1 Xiaoyu Wang,3 Shen Gao,3 Kehai Liu1

1Department 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 work

Background: 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

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