Lipid-polymer conjugates and liposomes

• US 5,395,619 A
• Filed: 03/03/1993
• Issued: 03/07/1995
• Est. Priority Date: 03/03/1993
• Status: Expired due to Term

• Current Assignee: Liposome Technology, Inc.
• Original Assignee: Liposome Technology, Inc.
• Inventors: Martin, Francis J., Woodle, Martin C., Lasic, Danilo D., Zalipsky, Samuel
• Primary Examiner(s): KISHORE, GOLLAMUDI S
• Application Number:
  US08/025,602
• Time in Patent Office: 734 Days
• Field of Search: 424/450, 428/402.2, 436/829, 525/340, 525/383, 525/410, 525/413, 525/419, 525/420, 264/4.1, 264/4.3, 264/4.33
• US Class Current: 424/450
• 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: Y10T 428/2984 Microcapsule with fluid core [includes liposome]

Abstract

A lipid-polymer conjugate for use in forming long-circulating liposomes is disclosed. The conjugate includes a vesicle-forming lipid having covalently attached to its polar head group, one of the polymers: polyvinylpyrrolidone, polyvinylmethylether, polyhydroxypropyl methacrylate, polyhydroxypropylmethacrylamide, polyhydroxyethyl acrylate, polymethacrylamide, polydimethylacrylamide, polymethyloxazoline, polyethyloxazoline, polyhydroxyethyloxazoline, polyhydroxypropyloxazoline, or polyaspartamide. A method for preparing liposomes containing the lipid-polymer conjugate is also disclosed.

Claims

1. A liposomal composition containing liposomes composed of vesicle-forming lipids and between 1-30 mole percent of a lipid-polymer conjugate composed of

a lipid having a hydrophobic moiety and a polar head group, and

covalently attached to the lipid head group, a homopolymer chain composed of polymethyloxazoline.

2. The conjugate of claim 1, wherein the homopolymer chain has degree of polymerization between about 20 to 150.

3. The conjugate of claim 1, wherein the vesicle-forming lipid is a phospholipid.

4. The conjugate of claim 3, wherein the vesicle-forming lipid is phosphatidylethanolamine.

5. A method of preparing liposomes characterized by an extended blood circulation time, comprising

adding to vesicle-forming lipids, between 1-30 mole percent of a lipid-polymer conjugate composed of a lipid having a hydrophobic moiety and a polar head group, and covalently attached to the lipid head group, a homopolymer chain composed of polymethyloxazoline,

forming liposomes containing said vesicle-forming lipids and said lipid-polymer conjugate, and containing a pharmaceutical compound in entrapped form, and

sizing the liposomes to a selected size in the size range between about 0.05 to 0.5 microns,

where the added conjugate is effective to extend the circulation time of the liposomes when compared to liposomes prepared in the absence of said conjugate.

6. The method of claim 5, wherein the added lipid-polymer conjugate is effective to reduce the electrophoretic mobility of the liposomes with respect to the same liposomes in which phosphatidylglycerol is substituted for the added conjugate.