DISPOSITION KINETICS OF LIPOSOMES MODIFIED WITH SYNTHETIC AMINOGLYCOLIPIDS IN RATS

Positively charged methyl-2-amino-6-palmitoyl-D-glycosides (PGLNs), i.e., derivatives of glucose (PGlcN), galactose (PGalN) and mannose (PManN), were synthesized to replace toxic stearylamine (SA) and were incorporated into liposomes. Methyl-6-palmitoyl glycosides (PGLs), namely, derivatives of glucose (PGlc), galactose (PGal) and mannose (PMan), were also synthesized for comparison with PGLN liposomes. PGLN and PGL liposomes newly prepared by extrusion were used to investigate their disposition kinetics in rats. The zeta potentials of liposomes, all of which contain 20 mol% of PGLN and have a diameter of about 200 nm, were about 10 mV in PBS. Those of egg PC/cholesterol and PGLN liposomes had small negative zeta potentials. These PGLN liposomes showed no hemolytic activity and no toxicity in the experimental concentration range. PGLN and PGL liposomes have the same stability as egg PC/cholesterol liposomes in rat serum. PGLNs prolonged the elimination of liposomes from the blood circulation and decreased the hepatic uptake of liposomes, while PGLs showed no effects. It was suggested that the positive charge on PGLNs is one important factor for the prolongation of the residency of liposomes in the blood circulation.