Cationic phospholipids forming cubic phases: lipoplex structure and transfection efficiency.

The transfection activity and the phase behavior of two novel cationic O-alkyl-phosphatidylcholines, 1,2-dioleoyl-sn-glycero-3-hexylphosphocholine (C6-DOPC) and 1,2-dierucoyl-sn-glycero-3-ethylphosphocholine (di22:1-EPC), have been examined with the aim of more completely understanding the mechanism of lipid-mediated DNA delivery. Both lipids form cubic phases: C6-DOPC in the entire temperature range from −10 to 90 °C, while di22:1-EPC exhibits an irreversible lamellar−cubic transition between 50 and 70 °C on heating. The lipoplexes formed by C6-DOPC arrange into hexagonal phase, while the lipoplexes of di22:1-EPC are lamellar. Both lipids exhibit lower transfection activity than the lamellar-forming 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine (EDOPC). Thus, for the studied cationic phospholipid-DNA systems, the lipoplex phase state is a factor that does not seem to correlate with transfection activity. The parameter that exhibits better correlation with the transfection activity within the present data...