Degradable copolymer based on amphiphilic N-octyl-N-quatenary chitosan and low-molecular weight polyethylenimine for gene delivery.
Int J Nanomedicine
; 7: 5339-50, 2012.
Article
em En
| MEDLINE
| ID: mdl-23071395
ABSTRACT
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.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Polietilenoimina
/
DNA
/
Transfecção
/
Quitosana
/
Nanocápsulas
Limite:
Humans
Idioma:
En
Revista:
Int J Nanomedicine
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
China