title: Gene carriers based on hexanediol diacrylate linked oligoethylenimine: effect of chemical structure of polymer on biological properties.
abstract: 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.
authors.affiliation: Department of Pharmacy, Center of Drug Research, Pharmaceutical Biology-Biotechnology, Ludwig Maximilian University, Butenandtstrasse 5-13, D-81377 Munich, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Kloeckner
authors.forename: Stefano
authors.initials: S
authors.lastname: Bruzzano
authors.forename: Manfred
authors.initials: M
authors.lastname: Ogris
authors.forename: Ernst
authors.initials: E
authors.lastname: Wagner
mesh_terms: 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
chemical_list: D000179:Acrylates; D011108:Polymers; D011094:Polyethyleneimine; D004247:DNA; C020355:1,6-hexanediol diacrylate