Gene carriers based on hexanediol diacrylate linked oligoethylenimine: effect of chemical structure of polymer on biological properties.
Two biodegradable polycations based on hexanediol diacrylate linked oligoethylenimine (OEI) were synthesized by applying different reaction temperatures, 20 degrees C (LT-OEI-HD) and 60 degrees C (HT-OEI-HD). Their structural properties were analyzed by NMR, FTIR, and SEC/MALLS (size exclusion chromatography coupled with multiangle laser light scattering detection). Reaction temperature strongly influenced molecular weight and ester/amide ratio and thus resulted in polycations with different biological activities and degradation profiles. LT-OEI-HD was an ester-based polycation of 8.7 kDa which degraded rapidly at pH 7 and pH 9 respectively. HT-OEI-HD had a molecular weight of 26.6 kDa, was mainly based on amides, and degraded more slowly than LT-OEI-HD. Both polymers mediated gene transfer as efficiently as linear polyethylenimine of 22 kDa in two cell lines while being less toxic at their optimal conjugate/plasmid (C/P) ratios. LT-OEI-HD needed higher C/P ratios for gene delivery; however, it was significantly less toxic than HT-OEI-HD.
Kloeckner
Julia
J
Department of Pharmacy, Center of Drug Research, Pharmaceutical Biology-Biotechnology, Ludwig Maximilian University, Butenandtstrasse 5-13, D-81377 Munich, Germany.
Bruzzano
Stefano
S
Ogris
Manfred
M
Wagner
Ernst
E
D020341:Absorbable Implants; D000179:Acrylates / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D051379:Mice; D015394:Molecular Structure; D008970:Molecular Weight; D011094:Polyethyleneimine / Q000737:chemistry / Q000378:metabolism; D011108:Polymers / Q000737:chemistry / Q000378:metabolism; D014162:Transfection
D000179:Acrylates; D011108:Polymers; D011094:Polyethyleneimine; D004247:DNA; C020355:1,6-hexanediol diacrylate