Liposomes containing active agents aggregated with lipid surfactants

• US 5,827,533 A
• Filed: 02/06/1997
• Issued: 10/27/1998
• Est. Priority Date: 02/06/1997
• Status: Expired due to Term

• Current Assignee: Duke University
• Original Assignee: Duke University
• Inventors: Needham, David
• Primary Examiner(s): Kishore, Gollamudi S.
• Application Number:
  US08/795,100
• Time in Patent Office: 628 Days
• Field of Search: 424/450, 424/1.21, 424/9.32, 424/9.51
• US Class Current: 424/450
• CPC Class Codes: A61K 9/1075 Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers A61K9/0026 takes precedence
• CPC Class Codes: A61K 9/1271 Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers liposome as conjugate A61K47/6911

Abstract

Liposomes contain active agents which are aggregated with a lipid surfactant. The composition of the liposome membrane stabilizes the membrane against the disruptive effects of the active agent-surfactant aggregate contained therein.

Claims

1. A liposome containing an active agent, comprising:

a liposome having a lipid bilayer membrane comprising vesicle-forming phospholipid and cholesterol, where the combination of phospholipid and cholesterol is the primary lipid source in the membrane, said lipid bilayer membrane containing from 3 mole percent to 60 mole percent cholesterol; and

an active agent aggregated with lipid surfactant to form micelles said micelles entrapped within the interior space of the liposome;

wherein said cholesterol inhibits fusion of the liposome membrane with the micelles entrapped therein, compared to fusion that would occur in the absence of cholesterol.

2. A liposome according to claim 1, wherein said lipid surfactant aggregated with said active agent is a lysolipid.

3. A liposome according to claim 1, wherein said lipid surfactant aggregated with said active agent is lysophosphatidylcholine.

4. A liposome according to claim 1, wherein the liposome membrane contains about 3 mole percent cholesterol.

5. A liposome according to claim 1, wherein said active agent is a pharmacologically active agent, a diagnostic agent, or a nutritional agent.

6. A liposome according to claim 1, wherein said active agent is pharmacologically active agent selected from the group consisting of antineoplastic agents, anti-inflammatory agents, immunosuppressive agents, antibiotic agents and anti-infective agents.

7. A liposome preparation comprising a plurality of liposomes according to claim 1.

8. A liposome according to claim 1 wherein the liposome membrane contains from about 3 mole percent cholesterol to about 40 mole percent cholesterol.

9. A liposome according to claim 1 wherein the liposome membrane contains less than about 40 mole percent cholesterol.

10. A liposome according to claim 1 wherein the liposome membrane contains less than about 20 mole percent cholesterol.

11. A liposome according to claim 1 wherein the liposome membrane contains from about 3 mole percent cholesterol to about 10 mole percent cholesterol.

12. A liposome according to claim 1 wherein said liposome is a unilamellar liposome.