Highly efficient gene transfer with degradable poly(ester amine) based on poly(ethylene glycol) diacrylate and polyethylenimine in vitro and in vivo.
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.
School of Agricultural Biotechnology, Seoul National University, Seoul 151-742, Korea.
Mi Ran
MR
Park
Hyon Woo
HW
Kim
Chang Sun
CS
Hwang
Ki Ok
KO
Han
Yun Jaie
YJ
Choi
Soo Chang
SC
Song
Myung Haing
MH
Cho
Chong Su
CS
Cho
D000280:Administration, Inhalation; D000818:Animals; D016923:Cell Death; D045744:Cell Line, Tumor; D002470:Cell Survival; D004247:DNA / Q000008:administration & dosage / Q000378:metabolism; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D010316:Particle Size; D011073:Polyamines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000378:metabolism*; D011091:Polyesters / Q000008:administration & dosage / Q000138:chemical synthesis / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000378:metabolism*; D011094:Polyethyleneimine / Q000008:administration & dosage / Q000378:metabolism*; D013499:Surface Properties; D013997:Time Factors; D014018:Tissue Distribution; D014162:Transfection / Q000379:methods*
D011073:Polyamines; D011091:Polyesters; C516446:poly(caprolactone-block-ethyleneimine); C437167:poly(ethylene glycol)diacrylate; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D004247:DNA