title: Synthesis, characterization and transfection activity of new saturated and unsaturated cationic lipids.
abstract: We synthesized new cationic lipids, analogue to N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA) and 1,2-dimyristyloxypropyl-3-dimethyl-hydroxyethylammonium bromide (DMRIE), in order to compare those containing a dodecyl chain with those having a relatively long chain with two or five double bonds, such as squalenyl and dihydrofarnesyl derivatives, or complex saturated structures, such as squalane derivatives. The fusogenic helper lipid dioleoylphosphatidylethanolamine (DOPE) was added to cationic lipids to form a stable complex. Liposomes composed of 50:50 w/w cationic lipid/DOPE were prepared and incubated with plasmidic DNA at various charge ratios and the diameter and zeta potential of the complexes were measured. The surface charge of the DNA/lipid complexes can be controlled by adjusting the cationic lipid/DNA ratio. Finally, we tested the in vitro transfection efficiency of the cationic lipid/DNA complexes using different cell lines. The transfection efficiency was highest for the dodecyloxy derivative containing a single hydroxyethyl group in the head, followed by the dodecyloxy and the farnesyloxy trimethylammonium derivatives. Instead the C27 squalenyl and C27 squalanyl derivatives resulted inactive.
authors.affiliation: Dipartimento di Scienza e Tecnologia del Farmaco, Università di Torino, Via Pietro Giuria 9, 10125 Torino, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Arpicco
authors.forename: Silvana
authors.initials: S
authors.lastname: Canevari
authors.forename: Maurizio
authors.initials: M
authors.lastname: Ceruti
authors.forename: Enrico
authors.initials: E
authors.lastname: Galmozzi
authors.forename: Flavio
authors.initials: F
authors.lastname: Rocco
authors.forename: Luigi
authors.initials: L
authors.lastname: Cattel
mesh_terms: D000818:Animals; D016466:CHO Cells; D002412:Cations; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000737:chemistry; D006801:Humans; D008055:Lipids / Q000096:biosynthesis / Q000138:chemical synthesis* / Q000737:chemistry / Q000235:genetics; D008081:Liposomes / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry* / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D014162:Transfection
chemical_list: D002412:Cations; D008055:Lipids; D008081:Liposomes; D010714:Phosphatidylethanolamines; D000644:Quaternary Ammonium Compounds; C054005:N-(1-(2,3-dioleyloxy)propyl)-N,N,N-trimethylammonium; C087276:(3-dimyristyloxypropyl)(dimethyl)(hydroxyethyl)ammonium; C094877:dioleoyl phosphatidylethanolamine; D004247:DNA