Star-shaped poly(ethylene glycol)-block-polyethylenimine copolymers enhance DNA condensation of low molecular weight polyethylenimines.
Star-shaped poly(ethylene glycol)-block-polyethylenimine [star-(PEG-b-PEI)] significantly enhance plasmid DNA condensation of low molecular weight (MW) PEIs. The star-block copolymers were prepared via a facile synthesis route using hexamethylene diisocyanate as linker between PEG and PEI blocks. NMR and FT-IR spectroscopy confirmed the structures of intermediately activated PEG and final products. Furthermore, the copolymers were characterized by size exclusion chromatography, static light scattering, and viscosimetry. Their molecular weights (M(w) 19-26 kDa) were similar to high MW PEI (25 kDa). Thermoanalytical investigations (thermogravimetric analysis, differential scanning calorimetry) were also performed and verified successful copolymer synthesis. DNA condensation with the low MW PEIs (800 and 2000 Da) and their 4- and 8-star-block copolymers was studied using atomic force microscopy, dynamic light scattering, zeta-potential measurements, and ethidium bromide (EtBr) exclusion assay. It was found that low MW PEIs formed huge aggregates (500 nm to 2 microm) in which DNA is only loosely condensed. By contrast, the star-block copolymers yielded small (80-110 nm), spherical and compact complexes that were stable against aggregation even at high ionic strength and charge neutrality. Furthermore, as revealed in the EtBr exclusion assay these star-block copolymers exhibited a DNA condensation potential as high as high MW PEI. Since these star-(PEG-block-PEI) copolymers are composed of relatively nontoxic low MW PEI and biocompatible PEG, their potential as gene delivery agents merits further investigations.
Petersen
Holger
H
Department of Pharmaceutics and Biopharmacy, Philipps-University of Marburg, Ketzerbach 63, D-35032 Marburg, Germany.
Kunath
Klaus
K
Martin
Alison L
AL
Stolnik
Snjezana
S
Roberts
Clive J
CJ
Davies
Martyn C
MC
Kissel
Thomas
T
D001672:Biocompatible Materials / Q000737:chemistry; D004247:DNA / Q000737:chemistry*; D018014:Gene Transfer Techniques; D008970:Molecular Weight; D010957:Plasmids / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011094:Polyethyleneimine / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship
D001672:Biocompatible Materials; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D004247:DNA