Biodegradable poly(ethylenimine) for plasmid DNA delivery.
Poly(ethylenimine) (PEI) has been known as an efficient gene carrier with the highest cationic charge potential. High transfection efficiency of PEI, along with its cytotoxicity, strongly depends on the molecular weight. Synthesis of cationic copolymers derived from the low molecular weight of PEI and hydrophilic poly(ethylene glycol) (PEG), which are water soluble and degradable under physiological conditions, was investigated for plasmid delivery. Hydrophilic PEG is expected to reduce the toxicity of the copolymer, improve the poor solubility of the PEI and DNA complexes, and help to introduce degradable bonds by reaction with the primary amines in the PEI. Considering the dependence of transfection efficiency and cytotoxicity on the molecular weight of the PEI, high transfection efficiency is expected from an increased molecular weight of the copolymer and low cytotoxicity from the introduction of PEG and the degradation of the copolymer into low molecular weight PEIs. Reaction conditions were carefully controlled to produce water soluble copolymers. Results from a gel retardation assay and zetapotentiometer indicated that complete neutralization of the complexes was achieved at the charge ratios of copolymer/pSV-beta-gal plasmid from 0.8 to 1.0 with the mean particle size of the polyplexes ranging from 129.8+/-0.9 to 151.8+/-3.4 nm. In vitro transfection efficiency of the synthesized copolymer increased up to three times higher than that of starting low molecular weight PEI, while the cell viability was maintained over 80%.
Ahn
Cheol-Hee
CH
Center for Controlled Chemical Delivery, Department of Pharmaceutics and Pharmaceutical Chemistry, Biomedical Polymers Research Building, University of Utah, RM 205, 84112, Salt Lake City, UT, USA
Chae
Su Young
SY
Bae
You Han
YH
Kim
Sung Wan
SW
D002460:Cell Line / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004269:DNA, Bacterial / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods* / Q000706:statistics & numerical data; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D010957:Plasmids / Q000008:administration & dosage*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D011094:Polyethyleneimine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*
D004269:DNA, Bacterial; D011092:Polyethylene Glycols; D011094:Polyethyleneimine