Synthesis of novel biodegradable cationic polymer: N,N-diethylethylenediamine polyurethane as a gene carrier.
A new cationic polymer, N,N-diethylethylenediamine-polyurethane (DEDA-PU), bearing tertiary amines in the backbone and side chains, was synthesized and used as a nonviral vector for gene delivery. The DEDA-PU readily self-assembled with the plasmid DNA (pCMV-betagal) in water and buffer at physiological pH, as determined by agarose gel retardation, dynamic light scattering, zeta potential, atomic force microscopy (AFM), and restriction endonuclease protection assays. The results revealed that DEDA-PU was able to bind with plasmid DNA, yielding positively charged complexes with a size around 100 nm at a DEDA-PU/DNA ratio of 50/1 (w/w). The DEDA-PU/DNA complexes were able to transfect HEK 293 cells in vitro with an efficiency comparable to a well-known gene carrier [poly(2-dimethylaminoethyl methacrylate), PDMAEMA]. The cytotoxicity of DEDA-PU was substantially lower than PDMAEMA. The degradation studies indicated that DEDA-PU degrades hydrolytically in 20 mM HEPES buffer at pH 7.4 with a half-life of approximately 60 h. This study shows that DEDA-PU holds promise as biodegradable polycations for gene delivery and is interesting candidate for further study.
Yang
Tsung-fu
TF
Department of Chemical Engineering, National Tsing-Hua University, Hsinchu 300, Taiwan, Republic of China.
Chin
Wei-kuo
WK
Cherng
Jong-yuh
JY
Shau
Min-da
MD
D002412:Cations; D002460:Cell Line; D005029:Ethylenediamines / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000378:metabolism; D018390:Gene Targeting / Q000379:methods*; D006801:Humans; D011108:Polymers / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000378:metabolism; D011140:Polyurethanes / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000378:metabolism; D014162:Transfection / Q000379:methods
D002412:Cations; D005029:Ethylenediamines; D011108:Polymers; D011140:Polyurethanes; C477544:N,N-diethylethylenediamine