A biodegradable poly(ester amine) based on polycaprolactone and polyethylenimine as a gene carrier.
The aim of research was to develop and optimize delivery systems for plasmid DNA (pDNA) based on biodegradable polymers, in particular, poly(ester amine)s (PEAs), suitable for non-viral gene therapy. Poly(ester amine)s were successfully synthesized by Michael addition reaction between polycaprolactone (PCL) diacrylate and low molecular weight polyethylenimine (PEI). PEA/DNA complexes showed effective and stable DNA condensation with the particle sizes below 200nm, implicating its potential for intracellular delivery. PEAs showed controlled degradation and were essentially non-toxic in all three cells (293T: Human kidney carcinoma, HepG2: Human hepatoblastoma and HeLa: Human cervix epithelial carcinoma cell lines) at higher doses in contrast to PEI 25K. PEAs also revealed much higher transfection efficiencies in three cell lines as compared to PEI 25K. The highest reporter gene expression was observed for PCL/PEI-1.2 (MW 1200) complex having transfection efficiency 15-25 folds higher than PEI 25K in vitro. Also PEA/DNA complexes successfully transfected cells in vivo after aerosol administration than PEI 25K. These PEAs can be used as most efficient polymeric vectors which provide a versatile platform for further investigation of structure property relationship along with the controlled degradation, significant low cytotoxicity and high transfection efficiency.
Arote
Rohidas
R
School of Agricultural Biotechnology, Seoul National University, Seoul 151-921, South Korea.
Kim
Tae-Hee
TH
Kim
You-Kyoung
YK
Hwang
Soon-Kyung
SK
Jiang
Hu-Lin
HL
Song
Ho-Hyun
HH
Nah
Jae-Woon
JW
Cho
Myung-Haing
MH
Cho
Chong-Su
CS
D001672:Biocompatible Materials / Q000737:chemistry*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D004337:Drug Carriers / Q000737:chemistry; D004587:Electrophoresis, Agar Gel; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D018625:Microscopy, Atomic Force; D015394:Molecular Structure; D010316:Particle Size; D011073:Polyamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D011094:Polyethyleneimine / Q000737:chemistry*; D014162:Transfection / Q000379:methods*
D001672:Biocompatible Materials; D004337:Drug Carriers; D011073:Polyamines; D011091:Polyesters; C516446:poly(caprolactone-block-ethyleneimine); C016240:polycaprolactone; D011094:Polyethyleneimine; D004247:DNA