Liposomes containing an entrapped compound in supersaturated solution

• US 20060159739A1
• Filed: 03/16/2006
• Published: 07/20/2006
• Est. Priority Date: 01/28/2000
• Status: Active Grant

• Current Assignee: Danilo D. Lasic, Robert M. Abra, Tal Peleg-Schulman, Yechezkel Barenholz
• Original Assignee: Danilo D. Lasic, Robert M. Abra, Tal Peleg-Schulman, Yechezkel Barenholz
• Inventors: Peleg-Schulman, Tal, Barenholz, Yechezkel, Lasic, Danilo D., Abra, Robert M.
• Granted Patent: US 8,062,662 B2
• Time in Patent Office: Days
• US Class Current: 424/450
• CPC Class Codes: A61K 33/243 Platinum; Compounds thereof
• 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: A61K 9/1277 Processes for preparing; Proliposomes
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

A liposome composition having a compound entrapped in a supersaturated solution and method for preparing such a composition are described.

Claims

1. A method for preparing liposomes having an entrapped compound in the form of a supersaturated solution, comprising:

selecting a compound having room temperature water solubility capable of exhibiting at least a two-fold increase in response to a condition selected from the group consisting of;

(i) increasing solvent temperature, (ii) adding a co-solvent, and (iii) changing solvent pH;

preparing from a supersaturated solution of the compound liposomes at selected size intervals;

analyzing said liposomes for the presence or absence of precipitated compound; and

based on said analyzing, selecting liposomes of a size that corresponds to liposomes having no entrapped precipitated compound.

2. The method of claim 1, wherein selecting the liposomes comprises selecting liposomes that have a liposome size of between about 60 nm to about 1000 nm.

3. The method of claim 1, wherein preparing the liposomes comprises preparing liposomes at size intervals between about 60 to about 1000 nm.

4. The method of claim 1, wherein preparing the liposomes comprises preparing liposomes at size intervals between about 70 nm to about 500 nm.

5. The method of claim 1, wherein said preparing liposomes comprises preparing a solution of lipids.

8. The method of claim 1, further comprising removing from an external liposome suspension medium the condition selected to maintain the compound above its room temperature solubility.

6. The method of claim 6, wherein the preparing comprises preparing a solution of lipids that comprises a lipid derivatized with a hydrophilic polymer.

7. The method of claim 6, wherein the preparing comprises preparing a solution of lipids effective to form a rigid lipid bilayer.

9. A method for preparing liposomes which contain a supersaturated solution of a compound, comprising:

preparing an aqueous supersaturated solution of a compound;

hydrating a lipid film or a lipid solution with said supersaturated solution of the compound to form liposomes;

sizing the liposomes to selected sizes;

analyzing the liposomes at each size for the presence or absence of precipitated compound; and

based on said analyzing, selecting liposomes having a size that corresponds to liposomes having no precipitated compound.