title: Synthesis and characterization of chemically condensed oligoethylenimine containing beta-aminopropionamide linkages for siRNA delivery.
abstract: Polyethylenimines (PEI) are often inefficient in gene knockdown experiments with small interfering RNA (siRNA), presumably due to the strong complexing properties. A more efficient and potentially degradable oligoethylenimine-based carrier was synthesized by the condensation of 800 molecular weight PEI oligomers with hexanedioldiacrylate. Reaction conditions were chosen such that Michael reaction occurs followed by complete N-acylation of all residual ester bonds resulting in beta-aminopropionamide linkage sites and an average molecular weight of 30,000. Based on NMR analysis, these conditions produced 38% tertiary amides and 62% secondary amides, with about 2% residual carboxylate, presumably from hydrolysis. The ionizable equivalent weight of the carrier increased to 51, compared to a value of 43 for standard PEI. Sensible in vitro knockdown of the luciferase gene in stably transfected HUH7 cells, up to 80% in comparison to non-specific siRNA, demonstrated its suitability for siRNA delivery.
authors.affiliation: Departments of Advanced Drug Delivery, Abbott Laboratories, North Chicago, IL, USA. peter.tarcha@abbott.com <peter.tarcha@abbott.com>
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Tarcha
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Pelisek
authors.forename: Thomas
authors.initials: T
authors.lastname: Merdan
authors.forename: Jan
authors.initials: J
authors.lastname: Waters
authors.forename: Kent
authors.initials: K
authors.lastname: Cheung
authors.forename: Katharina
authors.initials: K
authors.lastname: von Gersdorff
authors.forename: Carsten
authors.initials: C
authors.lastname: Culmsee
authors.forename: Ernst
authors.initials: E
authors.lastname: Wagner
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry; D001672:Biocompatible Materials / Q000138:chemical synthesis* / Q000737:chemistry; D045744:Cell Line, Tumor; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010316:Particle Size; D011094:Polyethyleneimine / Q000138:chemical synthesis* / Q000737:chemistry; D034741:RNA, Small Interfering / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013055:Spectrophotometry, Infrared; D014162:Transfection / Q000379:methods*
chemical_list: D000577:Amides; D001672:Biocompatible Materials; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D011094:Polyethyleneimine; D008156:Luciferases