Liposomes with enhanced circulation time

• US 4,837,028 A
• Filed: 12/24/1986
• Issued: 06/06/1989
• Est. Priority Date: 12/24/1986
• Status: Expired due to Term

• Current Assignee: Liposome Technology, Inc.
• Original Assignee: Liposome Technology, Inc.
• Inventors: Allen, Theresa M.
• Primary Examiner(s): Lovering, Richard D.
• Application Number:
  US06/946,415
• Time in Patent Office: 895 Days
• Field of Search: 428/402.2, 424/450, 436/829
• US Class Current: 424/1.21
• CPC Class Codes: A61K 9/1271 Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers liposome as conjugate A61K47/6911
• CPC Class Codes: Y10S 436/829 Liposomes, e.g. encapsulation
• CPC Class Codes: Y10T 428/2984 Microcapsule with fluid core [includes liposome]

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).

Claims

1. 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.

2. The composition of claim 1, wherein the liposomes have a size distribution produced by liposome extrusion through a 0.4 micron polycarbonate filter.

3. The composition of claim 1, wherein the membrane-rigidifying agent is predominantly PC with saturated acyl chains.

4. 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.

5. 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.