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

Content Provider	Europe PMC
Author	Liu, Chengchu Zhu, Qing Wu, Wenhui Xu, Xiaolin Wang, Xiaoyu Gao, Shen Liu, Kehai
Copyright Year	2012
Abstract	BackgroundChitosan 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).MethodsWe 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.ResultsThe 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.ConclusionOTMCS–PEI was a potential candidate as a safe and efficient gene vector for gene therapy.
ISSN	11769114
Journal	International Journal of Nanomedicine
Volume Number	7
PubMed Central reference number	PMC3469101
PubMed reference number	23071395
e-ISSN	11782013
DOI	10.2147/ijn.s36179
Language	English
Publisher	Dove Medical Press
Publisher Date	2012-10-08
Access Restriction	Open
Rights License	This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. © 2012 Liu et al, publisher and licensee Dove Medical Press Ltd.
Subject Keyword	nonviral gene vector polyethylenimine transfection efficiency cytotoxicity
Content Type	Text
Resource Type	Article
Subject	Nanoscience and Nanotechnology Organic Chemistry Drug Discovery Medicine Biomaterials Biophysics Bioengineering Pharmaceutical Science