GAS-CONTAINING LIPOSOMES

• US 20080175893A1
• Filed: 10/16/2007
• Published: 07/24/2008
• Est. Priority Date: 10/16/2006
• Status: Active Grant

• Current Assignee: Northwestern University, Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Northwestern University
• Inventors: MacDonald, Robert C., Kee, Patrick, Huang, Shaoling, McPherson, David
• Granted Patent: US 7,976,743 B2
• Time in Patent Office: Days
• US Class Current: 424/450
• CPC Class Codes: A61K 9/0009 involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis microelectromechanical systems A61K9/0097
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61K 9/1277 Processes for preparing; Proliposomes
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: Y10S 977/907 Liposome

Abstract

The present invention provides gas-containing liposomes. In particular, the present invention provide methods of generating gas-containing liposomes where the gas is introduced under pressure, as well as gas-containing liposomes which contain a large volume of gas (e.g., 10 ul of gas per 5 mg of gas-containing liposomes). In certain embodiments, the gas-containing liposomes contain nitric oxide gas. In some embodiments, such nitric oxide containing liposomes are used to treat a medical condition that is treatable by nitric oxide gas (e.g., intimal hyperplasia).

Claims

1. A method of making a gas-containing liposome, comprising:

freezing under pressure, liposomes with gas, to generate a gas-liposome dispersion; and

thawing said gas-liposome dispersion to generate a plurality of gas-containing liposomes.

2. The method of claim 1, wherein pressure is released from said gas-liposome dispersion prior to said thawing.

3. The method of claim 1, wherein pressure is released from said gas-liposome dispersion during said thawing.

4. The method of claim 1, wherein pressure is released only after said thawing step.

5. The method of claim 1, wherein each of said gas-containing liposomes contain between 4-8 percent of said gas by volume.

6. The method of claim 1, wherein said gas-containing liposomes comprise at least 10 ul of gas per 5 mg of said gas-containing liposomes.

7. The method of claim 1, wherein said gas-containing liposomes comprise at least 20 ul of gas per 5 mg of said gas-containing liposomes.

8. The method of claim 1, wherein said gas is selected from air, nitric oxide, a perflourocarbon, argon, and carbon monoxide.

9. The method of claim 1, further comprising a therapeutic agent useful in the treatment of atheroclothesis.

10. The composition of claim 1, wherein said gas-containing liposomes further comprise a second gas, wherein said second gas is configured to regulate the release rate of said nitric oxide from said liposome.

11. A composition comprising a plurality of gas-containing liposomes, wherein said gas-containing liposomes comprise at least 15 ul of gas per 5 mg of said gas-containing liposomes.

12. The composition of claim 11, wherein said gas-containing liposomes comprise at least 15 ul of said gas per 5 mg of said liposomes.

13. The composition of claim 11, wherein said gas-containing liposomes comprise at least 30 ul of said gas per 5 mg of said liposomes.

14. The composition of claim 11, wherein said gas-containing liposomes further comprise an antibody configured for targeting said gas-containing liposomes to a specific target in vivo.

15. The composition of claim 11, wherein said gas-containing liposomes further comprise a second gas, wherein said second gas is configured to regulate the release rate of said gas from said liposome.

16. A method of treating a medical condition comprising:

administering a composition to a patient, wherein said composition comprises a plurality of liposomes, wherein said liposomes comprise gas;

wherein said patient has a medical condition that is at least partially treatable by said gas; and

wherein said administering is under conditions such that said gas is released in said patient.

17. The method of claim 16, wherein said gas is nitric oxide.

18. The method of claim 16, further comprising visualizing the location of said liposomes in said patient via ultrasound.

19. The method of claim 16, further comprising causing said nitric oxide gas to be released in said patient by subjecting said patient to a triggering therapy.

20. The method of claim 16, wherein said medical condition is a cardiovascular condition.

21. A method of treating a patient comprising:

administering a composition to a patient, wherein said composition comprises a plurality of liposomes, wherein said liposomes comprise gas and a therapeutic agent.

22. The method of claim 21, wherein said therapeutic agent comprises rosiglitazone.