Carrier comprising a vitamin E derivative

Patent metadata

Field	Value
Publication number	US-9545392-B2
Application number	US-201013260685-A
Country	US
Kind code	B2
Filing date	Mar 29, 2010
Priority date	Dec 19, 2007
Publication date	Jan 17, 2017
Grant date	Jan 17, 2017

Abstract

A pharmaceutical composition is provided comprising a vitamin E derivative, an anionic phopholipid-binding protein, an anionic phospholipid and a sterol. Also provided is a method for preparing a composition for delivering a cargo to a subject comprising a) forming liposomes from a vitamin E derivative, an anionic phospholipid-binding protein such as annexin, an anionic phospholipid such as phosphatidylserine and a sterol; and b) encapsulating the cargo in the liposomal composition.

First claim

The invention claimed is:

1. A pharmaceutical composition comprising a vitamin E derivative, an anionic phospholipid-binding protein, an anionic phospholipid and a sterol, wherein the vitamin E derivative, anionic phospholipid and sterol form a lipid membrane and wherein the anionic phospholipid-binding protein is bound to the surface of the lipid membrane.

2. The composition according to claim 1 , further comprising cargo to be transported.

3. The composition according to claim 1 , wherein the vitamin E derivative is tocopherol.

4. The composition according to claim 1 , wherein the anionic phospholipid-binding protein is an annexin.

5. The composition according to claim 1 , wherein the anionic phospholipid is phosphatidylserine.

6. The composition according to claim 1 , wherein the sterol is cholesterol or 6-ketocholestanol.

7. The composition according to claim 1 , wherein the vitamin E derivative is 0.1-20% of the lipid membrane components.

8. The composition according to claim 1 , wherein the anionic phospholipid is 5-20% of the lipid membrane components.

9. The composition according to claim 1 , wherein the sterol is 15-30% of the lipid membrane components.

10. The composition according to claim 1 further comprising an additional phospholipid, and wherein the additional phospholipid is 30-80% of the lipid membrane components.

11. The composition according to claim 1 further comprising an additional phospholipid, and wherein the relative amount of each component is: vitamin E derivative: 0.1-20%; anionic phospholipid: 5-20%; sterol: 15-30%; additional phospholipid: 30-80% respectively, of the lipid membrane components.

12. The composition according to claim 2 , wherein the cargo is alpha-bungarotoxin.

13. A method for preparing a composition for delivering a cargo to a subject comprising a) forming liposomes from a vitamin E derivative, an anionic phospholipid-binding protein, an anionic phospholipid and a sterol, wherein the anionic phospholipid-binding protein is bound to the surface of the lipid membrane; and b) encapsulating the cargo in the liposomal composition.

14. The method according to claim 13 , wherein the phospholipid concentration is 20 mg/ml or more when the cargo is encapsulated.

15. The method according to claim 13 , wherein the cargo is encapsulated by being present at the time of liposome formation, or by electroporation, freeze-thawing, sonication or vortexing.

16. A method of delivering an agent across the blood brain barrier or across the blood retinal barrier, comprising administering the agent to a patient in need thereof, in combination with the pharmaceutical composition according to claim 1 .

17. A method of delivery of an agent to the posterior region of the eye comprising administering the agent to an eye in combination with the pharmaceutical composition according to claim 1 .

18. A method of delivery of an agent to the central nervous system, comprising administering the agent to a patient in need thereof, in combination with the pharmaceutical composition according to claim 1 .

19. A method of labeling the retinal vasculature of a subject, comprising administering alpha-bungarotoxin (αBT) to the eye of a subject.

20. The composition according to claim 1 , wherein the vitamin E derivative is tocopherol, the anionic phospholipid-binding protein is an annexin, the anionic phospholipid is phosphatidylserine, and the sterol is cholesterol or 6-ketocholestanol.

Assignees

• Cordeiro Francesca
• MOSS Stephen
• Coxon Katy
• Duggan James
• Ucl Business Plc

Inventors

• Cordeiro Francesca
• MOSS Stephen
• Coxon Katy
• Duggan James

Classifications

• A61P27/00

  Drugs for disorders of the senses · CPC title

• A61K9/1271

  Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers (liposomes as conjugates {A61K47/6911}) · CPC title

• A61K38/1709

  from mammals · CPC title

• A61K9/0048

  Eye, e.g. artificial tears · CPC title

• A61K31/355 Primary

  Tocopherols, e.g. vitamin E · CPC title