Gangliosides reduce leakage of aqueous-space markers from liposomes in the presence of human plasma.
We have studied the role of glycolipids in reducing leakage of aqueous-space markers from liposomes, composed primarily of egg phosphatidylcholine, in the presence of human plasma. Liposomes were either small unilamellar (SUV) or large unilamellar (LUV). Leakage of liposome contents as affected by the incorporation into the liposomal bilayer of mono-, di-, or trisialogangliosides (GM, GD, GT) at different molar ratios in the presence or absence of cholesterol was examined. Leakage from liposomes decreased with increasing ganglioside sialic acid. Asialogangliosides had no effect on calcein leakage in the presence of plasma. The stabilizing effect of gangliosides and cholesterol was synergistic, and SUV containing 10 mol% GT and 33 mol% cholesterol had a half-life for leakage of calcein in plasma at 37 degrees C approaching 24 hours. LUV in the presence of plasma retained their contents longer than SUV, and gangliosides had an additional stabilizing effect. Phosphatidylserine and sulfatides were also capable of substituting for gangliosides in stabilizing liposomes to plasma-induced leakage. It appears that gangliosides stabilize liposomes in plasma at least in part through their ability to impart surface negative charge.
D001798:Blood Proteins / Q000502:physiology; D002021:Buffers; D002784:Cholesterol / Q000378:metabolism; D005452:Fluoresceins / Q000378:metabolism; D005732:Gangliosides / Q000378:metabolism*; D006801:Humans; D008081:Liposomes / Q000378:metabolism*; D010539:Permeability; D010949:Plasma; D013696:Temperature
D001798:Blood Proteins; D002021:Buffers; D005452:Fluoresceins; D005732:Gangliosides; D008081:Liposomes; D002784:Cholesterol; C007740:fluorexon