Liposomes composed of synthetic dialkyl cationic
lipids and zwitterionic
phospholipids such as
dioleoylphosphatidylethanolamine have been studied extensively as vehicles for gene delivery, but the broader potentials of these cationic
liposomes for
drug delivery have not. An understanding of
phospholipid-cationic
lipid interactions is essential for rational development of this potential. We evaluated the effect of the cationic
lipid DOTAP (N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium) on
liposome physical properties such as size and membrane domain structure. DSC (differential scanning calorimetry) showed progressive decrease and broadening of the phase transition temperature of
dipalmitoylphosphatidylcholine (DPPC) with increasing fraction of
DOTAP, in the range of 0.4-20 mol%.
Laurdan (6-dodecanolyldimethylamino-naphthalene), a
fluorescent probe of membrane domain structure, showed that
DOTAP and DPPC remained miscible at all ratios tested.
DOTAP reduced the size of spontaneously-forming PC-containing
liposomes, regardless of the acyl chain length and degree of saturation. The anionic
lipid DOPG (dioleoylphosphatidylglycerol) had similar effects on DPPC membrane fluidity and size. However,
DOTAP/
DOPC (50/50) vesicles were taken up avidly by OVCAR-3 human ovarian
tumor cells, in contrast to
DOPG/
DOPC (50/50)
liposomes. Overall,
DOTAP exerts potent effects on bilayer physical properties, and may provide advantages for
drug delivery.