Liposomes containing active agents

• US 6,296,870 B1
• Filed: 02/03/1998
• Issued: 10/02/2001
• Est. Priority Date: 02/06/1997
• Status: Expired due to Term

• Current Assignee: Duke University
• Original Assignee: Duke University
• Inventors: Sarpal, Ranjit S., Needham, David
• Primary Examiner(s): Kishore, Gollamudi S.
• Application Number:
  US09/017,984
• Time in Patent Office: 1,337 Days
• Field of Search: 424/450, 424/417, 424/1.21, 424/9.321, 424/9.51, 424/94.3, 935/54, 428/402.2
• 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 formulations are designed to maximize the amount of poorly water-soluble active agent that can be carried by the liposome. Liposomes containing active agent in the lipid bilayer of the liposome, and/or entrapped within the liposome interior space in a micellar preparation are described. Methods of making such liposomes are presented.

Claims

1. A liposome containing an active agent, wherein the lipid bilayer of the liposome comprises:

a) phospholipid;

b) an active agent associated with the lipid bilayer;

c) surfactant with a Critical Micelle Concentration (CMC) of about 1 millimolar or less, said surfactant contained in the lipid bilayer in an amount sufficient to increase the amount of active agent associated with the lipid bilayer, compared to that amount of active agent that would associate with the lipid bilayer in the absence of surfactant, wherein the active agent is aggregated with said surfactant to form micelles; and

d) from 3 mole percent to 60 mole percent of cholesterol present in the lipid bilayer in an amount sufficient to protect against the disruptive effects of the surfactant contained in the lipid bilayer,

wherein the lipid bilayer is unilaminar.

2. A liposome according to claim 1, wherein said phospholipid is stearoyloleoylphosphatidylcholine(SOPC).

3. A liposome according to claim 1, wherein said surfactant is a lysolipid.

4. A liposome according to claim 1, wherein said surfactant is a lysophosphatidylcholine.

5. A liposome according to claim 1, wherein said surfactant is monooleyolphosphatidylcholine(MOPC).

6. A liposome according to claim 1, wherein said active agent is paclitaxel.

7. A liposome according to claim 6, where paclitaxel is contained in the lipid bilayer in an amount of at least 10 mol % relative to SOPC.

8. A liposome according to claim 1, said lipid bilayer further comprising polymer-derivatized lipids.

9. A liposome according to claim 7, wherein said polymer is polyethylene glycol.

10. A liposome according to claim 1, wherein said phospholipid is stearoyloleoylphosphatidylcholine(SOPC) and said surfactant is monooleyolphosphatidylcholine(MOPC), and MOPC is present in an amount at least sufficient to provide a mole ratio of 8:

1 SOPC;

MOPC.