Method of lipid structure preparation

• US 20060121105A1
• Filed: 10/07/2005
• Published: 06/08/2006
• Est. Priority Date: 10/08/2004
• Status: Active Grant

• Current Assignee: Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. (Hebrew University of Jerusalem)
• Original Assignee: Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. (Hebrew University of Jerusalem)
• Inventors: Barenholz, Yechezkel, Garbuzenko, Olga
• Granted Patent: US 7,985,417 B2
• Time in Patent Office: Days
• US Class Current: 424/450
• CPC Class Codes: A61K 47/6907 the form being a microemulsion, nanoemulsion or micelle
• CPC Class Codes: A61K 47/6913 the liposome being modified on its surface by an antibody
• 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 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/32 against translation products of oncogenes
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)

Abstract

A method of inserting a lipid-linked moiety into a lipid assembly, such as a planar lipid monolayer or bilayer, a spherical lipid vesicle, a micelle, or an emulsion envelope monolayer is described. In the method, the lipid assembly and the lipid-linked moiety are contacted in the presence of microwave irradiation to permit the lipid-linked moiety to become associated with the lipid assembly. In one embodiment, the lipid assembly is a liposome and the lipid-linked moiety is a lipid-polymer. Compositions comprised of a lipid layer and of a lipid-linked moiety, prepared in accord with the method, are also described.

Claims

1. A method for inserting a lipid-linked moiety into a lipid assembly, comprising:

contacting a lipid assembly and a lipid-linked moiety in the presence of microwave energy effective to permit the lipid-linked moiety to become associated with said lipid assembly.

2. The method of claim 1, wherein said lipid assembly is a synthetic lipid assembly.

3. The method of claim 1, wherein said lipid assembly is a micelle.

4. The method of claim 1, wherein said lipid assembly contains a lipid bilayer.

5. The method of claim 1, wherein said lipid assembly contains a lipid monolayer.

6. The method of claim 1, wherein said lipid assembly is an emulsion.

7. The method of claim 1, wherein said lipid assembly is a liposome.

8. The method of claim 1, wherein said lipid assembly is comprised of vesicle-forming lipids.

9. The method of claim 8, wherein said vesicle-forming lipids have a phase transition temperature of greater than about 50°

C.

10. The method of claim 1, wherein said lipid-linked moiety is a lipid-polymer moiety.

11. The method of claim 10, wherein said lipid-linked moiety is a lipid-polyethylene glycol moiety.

12. The method of claim 1, wherein said lipid-linked moiety is a lipid-drug moiety.

13. The method of claim 1, wherein said lipid-linked moiety is a lipid-biological ligand moiety.

14. The method of claim 13, wherein said biological ligand is selected from the group consisting of a peptide, a protein, and a nucleic acid.

15. The method of claim 14, wherein said peptide or protein is an antibody or an antibody fragment.

16. The method of claim 13, wherein said biological ligand has binding affinity for a cell surface receptor.

17. The method of claim 1, wherein said lipid-linked moiety is a lipid-peptidomimetic moiety.

18. The method of claim 1, wherein said lipid assembly is a liposome containing an entrapped therapeutic agent.

19. The method of claim 18, wherein said lipid-linked moiety is a lipid-biological ligand moiety.

20. The method of claim 19, wherein said biological ligand has binding affinity for a cell surface receptor.

21. The method of claim 1, wherein said lipid-linked moiety is a lipid-carbohydrate moiety.

22. A lipid assembly, comprising a lipid layer and a lipid-linked moiety, said lipid assembly obtainable by the process of incubating said lipid layer and said lipid-linked moiety in the presence of microwave energy.

23. The lipid assembly of claim 22, wherein said lipid-linked moiety is a lipopolymer.

24. The lipid assembly of claim 22, wherein said lipid-linked moiety is a lipopolymer-ligand.

25. The lipid assembly of claim 22, wherein said lipid assembly is comprised of a monolayer.

26. The lipid assembly of claim 22, wherein said lipid-linked moiety is comprised of a lipid bilayer.

27. A method of preparing a liposome composition comprised of liposomes having a lipid-linked moiety associated with the liposomes'"'"' bilayer, comprising:

contacting a suspension of liposomes and a micellar suspension of a lipid-linked moiety in the presence of microwave energy effective to achieve association of the lipid-linked moiety with the liposomes.

28. The method of claim 27, wherein said liposomes have an entrapped therapeutic agent.

29. The method of claim 27, wherein said lipid-linked moiety is a lipid-polymer moiety.

30. The method of claim 27, wherein said lipid-linked moiety is a lipid-polyethylene glycol moiety.

31. The method of claim 27, wherein said lipid-linked moiety is a lipid-drug moiety.

32. The method of claim 27, wherein said lipid-linked moiety is a lipid-biological ligand moiety.

33. The method of claim 32, wherein said biological ligand is selected from the group consisting of a peptide, a protein, an a nucleic acid.

34. The method of claim 33, wherein said peptide or protein is an antibody or an antibody fragment.

35. The method of claim 32, wherein said biological ligand has binding affinity for a cell surface receptor.

36. The method of claim 27, wherein said lipid-linked moiety is a lipid-peptidomimetic moiety.

37. The method of claim 27, wherein said lipid-linked moiety is a lipid-carbohydrate moiety.