LIPID THERAPY

Abstract

A method including introducing into a blood stream a delipidated high density lipoprotein (HDL) and a bioactive agent. A composition including a delipidated high density lipoprotein (HDL) and an auxiliary agent in a form suitable for delivery into a blood vessel. A composition including Apo A1 comprising a hydrophobic ligand suitable to interact with cell surface binding sites. A composition including Apo A1 and an agent selected to one of increase the ATP-binding cassette protein 1 (ABCA1) transporter expression in macrophages and protect ABCA1 from thiol-mediated degradation.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

Features, aspects, and advantages of embodiments will become more thoroughly apparent from the following detailed description, appended claims, and accompanying drawings in which:

FIG. 1 shows a flow chart of a process for delipidating HDL from a sample of blood and infusing the delipidated HDL, which may further include an adjuvant.

FIG. 2A shows a schematic, top perspective view of an embodiment of a delipidation sub-module.

FIG. 2B shows a schematic, top perspective view of another embodiment of a delipidation sub-module.

FIG. 3 shows a schematic cross-sectional side view of a system for delipidating HDL and introducing the delipidated HDL, which may further include an adjuvant.

FIG. 4 shows a schematic cross-sectional side view of a system for withdrawing blood and implementing delipidation of HDL and introducing the delipidated HDL, which may further include an adjuvant.

FIG. 5 shows a schematic cross-sectional side view of a stent in a blood vessel.

FIG. 6 shows a schematic cross-sectional side view of a catheter assembly in a blood vessel.

FIG. 7 shows a schematic cross-sectional side view of another embodiment of a catheter assembly in a blood vessel.

FIG. 8 shows a schematic cross-sectional side view of another embodiment of a catheter assembly in a blood vessel.

FIG. 9 shows a schematic cross-sectional side view of another embodiment of a catheter assembly in a blood vessel.

FIG. 10 shows a schematic cross-sectional side view of another embodiment of a catheter assembly in a blood vessel.

FIG. 11 shows a cross-sectional side view of a needle suitable for use in the catheter assembly in FIG. 10.

Claims

1. A method comprising: introducing into a blood stream or tissue a delipidated high density lipoprotein (HDL) and a bioactive agent.

2. The method of claim 1, wherein introducing comprises systemically introducing.

3. The method of claim 1, wherein introducing comprises locally introducing.

4. The method of claim 1, wherein introducing comprises locally introducing to an ischemic area.

5. The method of claim 1, wherein introducing comprises introducing the delipidated HDL upstream from a treatment site.

6. The method of claim 1, wherein introducing comprises introducing to a peri-adventitial area.

7. The method of claim 6, further comprising introducing a gel-forming biomaterial to the peri-adventitial area.

8. The method of claim 1, wherein prior to introducing, the method comprises: withdrawing an amount of blood; anddelipidating HDL present in the blood.

9. The method of claim 8, wherein withdrawing, delipidating and introducing comprise a closed loop system.

10. The method of claim 9, wherein the closed loop system comprises a catheter assembly.

11. The method of claim 1, wherein the bioactive agent comprises at least one of an apolipoprotein A1 (Apo A1), a mutant form of Apo A1 and a mimetic peptide of Apo A1.

12. A composition comprising: a delipidated high density lipoprotein (HDL) and an auxiliary agent in a form suitable for delivery into a blood vessel.

13. The composition of claim 12, wherein the auxiliary agent comprises a property that will enhance the residence time of the HDL at a specific location within the blood vessel.

14. The composition of claim 12, wherein the auxiliary agent comprises a property that will stabilize an amphipatic helical structure of the HDL in situ.

15. The composition of claim 12, wherein the auxiliary agent comprises a property that will enhance the interaction between Apo A1 and cell surface binding sites.

16. The composition of claim 12, wherein the auxiliary agent comprises a property that will increase the solubility of free cholesterol and phospholipids in fully lipidated high density lipoproteins.

17. The composition of claim 12, wherein the auxiliary agent comprises a cross-linker of Apo A1.

18. A composition comprising: Apo-A1 comprising a hydrophobic ligand suitable to interact with cell surface binding sites.

19. The composition of claim 18, wherein the hydrophobic ligand is selected from the group consisting of elastin pentapeptide and lueucine-rich oligopeptide.

20. The composition of claim 18, wherein the hydrophobic ligand is selected from the group consisting of stearoyl, olyeol, and palmitoyl.

21. A composition comprising: Apo A1 and an agent selected to one of increase the ATP-binding cassette protein 1 (ABCA1) transporter expression in macrophages and protect ABCA1 from thiol-mediated degradation.

22. A method comprising: delivering to a treatment site within a lumen of a blood vessel, in a wall of the blood vessel, or beyond the blood vessel by a percutaneous transluminal route an agent comprising at least one of a delipidated HDL, an HDL-mimicking peptide having a property to bind cholesterol, and a cyclodextrin.

23. The method of claim 22, wherein locally delivering comprises placing a stent within the blood vessel, the stent comprising the agent as a coating on a body of the stent or as a portion of the body of the stent.

24. The method of claim 22, wherein prior to delivering the agent, the method comprises: occluding the blood vessel at a point upstream of a treatment site and a point downstream of the treatment site.

25. The method of claim 22, wherein prior to delivering the one of the cellular component and the conjugate, the method comprises at least partially occluding the blood vessel at a treatment site with a porous occlusion device, and delivering comprises delivering the agent through the porous occlusion device.

26. The method of claim 22, wherein prior to delivering the agent, the method comprises inserting an occlusion device into the blood vessel that at least partially occludes the blood vessel, and delivering comprises delivering the agent through the occlusion device.

27. The method of claim 26, wherein the occlusion device comprises a balloon assembly comprising a porous portion and delivering comprises delivering the one of the agent through the porous portion.

28. The method of claim 26, wherein the occlusion device comprises a sponge.

29. The method of claim 22, wherein the treatment site comprises a periadventitial area.

30. The method of claim 29, further comprising introducing a gel biomaterial to the periadvential area.