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Highly efficient gene transfer with degradable poly(ester amine) based on poly(ethylene glycol) diacrylate and polyethylenimine in vitro and in vivo
Author(s) -
Park Mi Ran,
Kim Hyon Woo,
Hwang Chang Sun,
Han Ki Ok,
Choi Yun Jaie,
Song Soo Chang,
Cho Myung Haing,
Cho Chong Su
Publication year - 2008
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.1139
Subject(s) - polyethylenimine , ethylene glycol , gene delivery , in vivo , polymer , amine gas treating , zeta potential , peg ratio , chemistry , in vitro , transfection , gene expression , polymer chemistry , microbiology and biotechnology , biophysics , nuclear chemistry , materials science , biochemistry , gene , organic chemistry , biology , nanotechnology , nanoparticle , finance , economics
Background Polyethylenimine (PEI) is toxic although it is one of the most successful and widely used gene delivery polymers with the aid of the proton sponge effect. Therefore, development of new novel gene delivery carriers having high efficiency with less toxicity is necessary. Methods In this study, a degradable poly(ester amine) carrier based on poly(ethylene glycol) diacrylate (PEGDA) and low molecular weight linear PEI was prepared. Furthermore, we compared the gene expression of the polymer/DNA complexes using two delivery methods: intravenous administration as an invasive method and aerosol as a non‐invasive method. Results The synthesized polymer had a relatively small molecular weight (MW = 7980) with 25 h half‐life in vitro . The polymer/DNA complexes were formed at an N/P ratio of 9. The particle sizes and zeta‐potentials of the complexes were dependent on N/P ratio. Compared to PEI 25K, the newly synthesized polymer exhibited high transfection efficiency with low toxicity. Poly(ester amine)‐mediated gene expression in the lung and liver was higher than that of the conventional PEI carrier. Interestingly, non‐invasive aerosol delivery induced higher gene expression in all organs compared to intravenous method in an in vivo mice study. Such an expressed gene via a single aerosol administration in the lung and liver remained unchanged for 7 days. Conclusions Our study demonstrates that poly(ester amine) may be applied as an useful gene carrier. Copyright © 2007 John Wiley & Sons, Ltd.