Abstract A composition of liposomes which contain an entrapped pharmaceutical agent and are characterized by: (a) liposome sizes predominantly between about 0.08 and 0.5 microns: (b) at least about 50 mole percent of a membrane-rigidifying component, such as sphingomyelin or neutral phospholipids with predominantly saturated acyl chains: and (c) between about 5-15 mole percent ganglioside G M1 . The liposomes show a blood/RES tissue distribution ratio, two hours after intravenous administration, which is substantially greater than the sum of the distribution ratios observed with similarly constructed liposome compositions containing the membrane-rigidifying agent alone and gangliosides alone. Also disclosed are methods for enhancing the blood/RES ratio of intravenously administered liposomes, and for assessing the effect of selected liposome components on in vivo uptake of liposomes by cells of the reticuloendothelial system (RES).
A liposome composition having an enhanced blood circulation time when administered intravenously, comprising liposomes which contain an entrapped pharmaceutical agent and are characterized by: (a) liposome sizes predominantly between about 0.08 and 0.5 microns, (b) at least about 50 mole percent of a membrane-rigidifying lipid component selected from the group consisting of sphingomyelin and neutral phospholipids with predominantly saturated acyl chains, and (c) between about 5-15 mole precent ganglioside G M1 .
Claim 2
Dependent Claim
72 words
A liposome composition having an enhanced blood circulation time when administered intravenously, comprising liposomes which contain an entrapped pharmaceutical agent and are characterized by: (a) liposome sizes predominantly between about 0.08 and 0.5 microns, (b) at least about 50 mole percent of a membrane-rigidifying lipid component selected from the group consisting of sphingomyelin and neutral phospholipids with predominantly saturated acyl chains, and (c) between about 5-15 mole precent ganglioside G M1 .
Claim 3
Dependent Claim
22 words
The composition of claim 1, wherein the liposomes have a size distribution produced by liposome extrusion through a 0.4 micron polycarbonate filter.
Claim 4
Dependent Claim
16 words
The composition of claim 1, wherein the membrane-rigidifying agent is predominantly PC with saturated acyl chains.
Claim 5
Dependent Claim
80 words
In a therapeutic drug treatment in which a drug is administered intravenously in a suspension of liposomes whose sizes are predominantly between about 0.08-0.5 microns, a method of extending the lifetime of liposomes in the bloodstream which comprises preparing the liposomes to contain: (a) at least about 50 mole percent of a membrane-rigidifying component selected from the group consisting of sphingomyelin and neutral phospholipids with predominantly saturated acyl chains, and (b) between about 5-15 mole percent ganglioside G M1 .
Claim 6
Dependent Claim
80 words
In a therapeutic drug treatment in which a drug is administered intravenously in a suspension of liposomes whose sizes are predominantly between about 0.08-0.5 microns, a method of extending the lifetime of liposomes in the bloodstream which comprises preparing the liposomes to contain: (a) at least about 50 mole percent of a membrane-rigidifying component selected from the group consisting of sphingomyelin and neutral phospholipids with predominantly saturated acyl chains, and (b) between about 5-15 mole percent ganglioside G M1 .
Claim 7
Dependent Claim
26 words
The method of claim 4, wherein the liposomes are predominantly oligolamellar and have a size distribution produced by liposome extrusion through a 0.4 micron polycarbonate filter.