Electrostatically mediated interactions between cationic lipid-DNA particles and an anionic surface

In an effort to model the interaction of lipid-based DNA delivery systems w ith anionic surfaces, such as a cell membrane, we have utilized microelectr ophoresis to characterize how electrokinetic measurements can provide infor mation on surface charge and binding characteristics. We have established t hat cationic lipids, specifically N-N-dioleoyl-N,N-dimethylammonium chlorid e (DODAC), incorporated into liposomes prepared with I,2-dioleoyl-i-glycero -3-phosphoethanolamine (DOPE) or 1,2-dioleoyl-sn-glycero-3-phosphocholine ( DOPC) at 50 mol%, change the inherent electrophoretic mobility of anionic l atex polystyrene beads. Self-assembling lipid-DNA particles (LDPs), prepare d at various cationic lipid to negative DNA phosphate charge ratios, effect ed no changes in bead mobility when the LDP charge ratio (+/-) was equal to or less than 1. Increasing the LDP concentration in a solution of 0.1% (w/ v) anionic beads resulted in a charge reversal effect when a net charge of LDP to total bead charge ratio (+/-) of 1:1 was observed. LDP formulations, utilizing either DOPE or DOPC, showed similar titration profiles with a ch arge reversal observed at a 1:1 net LDP to bead charge ratio (+/-). It was confirmed through centrifugation studies that the DNA in the LDP was associ ated with the anionic latex beads through electrostatic interactions. LDP b inding, rather than the binding of dissociated cationic lipids, resulted in the observed electrophoretic mobility changes of the anionic latex beads. (C) 1999 Academic Press.