Phospholipid-cationic lipid interactions: influences on membrane and vesicle properties.
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.
Campbell
R B
RB
Department of Molecular and Cellular Biophysics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Balasubramanian
S V
SV
Straubinger
R M
RM
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D002448:Cell Adhesion; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D008856:Microscopy, Fluorescence; D010743:Phospholipids / Q000737:chemistry*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D013050:Spectrometry, Fluorescence; D014407:Tumor Cells, Cultured / Q000737:chemistry
D005229:Fatty Acids, Monounsaturated; D008051:Lipid Bilayers; D008055:Lipids; D008081:Liposomes; D010743:Phospholipids; D000644:Quaternary Ammonium Compounds; C054005:N-(1-(2,3-dioleyloxy)propyl)-N,N,N-trimethylammonium; D015060:1,2-Dipalmitoylphosphatidylcholine; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane