Nanoparticle-Coated Medical Devices And Formulations For Treating Vascular Disease

• US 20100104506A1
• Filed: 01/05/2010
• Published: 04/29/2010
• Est. Priority Date: 08/16/2007
• Status: Abandoned Application

• Current Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories)
• Original Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories)
• Inventors: Ludwig, Florian Niklas, Astafieva, Irina, Hossainy, Syed Faiyaz Ahmed, Zhao, Li, Murase, Katsuyuki
• Application Number:
  US12/652,668
• Publication Number:
  US 20100104506A1
• Time in Patent Office: Days
• US Class Current: 424/1.110
• CPC Class Codes: A61K 9/1075 Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers A61K9/0026 takes precedence
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61K 9/51 Nanocapsules; Nanoparticles; nanotubes A61K9/0092; polymeric micelles A61K9/1075; polymersomes A61K9/1273; pure drug nanoparticles A61K9/14; drug nanoparticles with adsorbed surface modifiers A61K9/141; conjugates, e.g. between drug and non-active nanoparticles, A61K47/50; preparations for in vivo diagnosis A61K49/00; with radioactive substances A61K51/00
• CPC Class Codes: A61L 2300/624 Nanocapsules
• CPC Class Codes: A61L 2300/626 Liposomes, micelles, vesicles
• CPC Class Codes: A61L 2400/12 Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• 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: A61P 9/14 Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers

Abstract

Nanoparticle-coated medical devices, nanoparticle-containing formulations and methods of using for treating a vascular disease are disclosed. The medical device includes a coating that comprises a plurality of nanoparticles, wherein the nanoparticles comprise one or more bioactive agents encapsulated within, adhered to a surface of or integrated into the structure of the nanoparticles and further comprise one or more contrast enhancing agents encapsulated within, adhered to a surface of or integrated into the structure of the nanoparticles.

Claims

1. An implantable medical device comprising:

a coating that comprises a plurality of nanoparticles, wherein the nanoparticles comprise one or more bioactive agents encapsulated within, adhered to a surface of or integrated into the structure of the nanoparticles and further comprise one or more contrast enhancing agents encapsulated within, adhered to a surface of or integrated into the structure of the nanoparticles.

2. The implantable medical device according to claim 1, wherein the nanoparticles comprise micelles, liposomes, worm micelles, polymersomes, polymer particles or hydrogel particles.

3. The implantable medical device according to claim 2, wherein the micelle, liposome, worm micelle, polymerosome or polymer particle comprise an amphiphilic block co-polymer.

4. The implantable medical device according to claim 1, wherein the bioactive agent is selected from the group consisting of a corticosteroid, everolimus, an everolimus derivative, zotarolimus, a zotaralimus derivative, sirolimus, a sirolimus derivative, paclitaxel, biolimus A9, a bisphosphonate, ApoA1, a mutated ApoA1, ApoA1 milano, an ApoA1 mimetic peptide, an ABC A1 agonist, an anti-inflammatory agent, an anti-proliferative agent, an anti-angiogenic agent, a matrix metalloproteinase inhibitor and a tissue inhibitor of metalloproteinase.

5. The implantable medical device according to claim 1, wherein the one or more contrast enhancing agents are selected from the group consisting of iodine, barium, barium sulfate and gastrografin.

6. The implantable medical device according to claim 1, wherein the one or more contrast enhancing agents enhances one or more imaging modalities selected from the group consisting of optical, magnetic resonance, acoustic, ultra-sound, x-ray, gamma-radiation and radioactive-mediated imaging modalities.

7. The implantable medical device according to claim 1, wherein the nanoparticles further comprise a first functional group with binding affinity for endothelium operatively coupled to the surface of the nanoparticles.

8. The implantable medical device according to claim 7, wherein the first functional group comprises one or more first peptides, first proteins, first oligonucleotides or any combination thereof.

9. The implantable medical device according to claim 8, wherein the one or more first peptides comprise an RGD sequence or an antibody fragment.

10. The implantable medical device according to claim 8, wherein the one or more first proteins comprise an antibody or an affibody.

11. The implantable medical device according to claim 10, wherein the antibody is selected from the group consisting of an anti-intercellular adhesion molecule, an anti-vascular cellular adhesion molecule, an anti-integrin, an anti-platelet endothelial cell adhesion molecule, an anti-thrombomodulin, an anti-e-selectin, an anti-fibronectin, an anti-sialyl-Lewis[b] glycan, an anti-endothelial glycocalyx protein, an anti-cadherin or any combination thereof.

12. The implantable medical device according to claim 8, wherein the one or more first oligonucleotides comprise an aptamer.

13. The implantable medical device according to claim 7, wherein the nanoparticles further comprise a second functional group with binding affinity for surface-expressed molecules on dysfunctional endothelium operatively coupled to the surface of the nanoparticles.

14. The implantable medical device according to claim 13, wherein the second functional group is an aptamer.

15. The implantable medical device according to claim 14, wherein the aptamer comprises an anti-junction adhesion molecule or an anti-leukocyte adhesion molecule.

16. The implantable medical device according to claim 13, wherein the nanoparticles further comprise a third functional group with binding affinity for vascular cell wall components operatively coupled to the surface of the nanoparticles.

17. The implantable medical device according to claim 16, wherein the third functional group comprises one or more lipids, third peptides, third proteins, third oligonucleotides or any combination thereof.

18. The implantable medical device according to claim 17, wherein the one or more lipids are selected from the group consisting of an oleic acid, a stearic acid and an oleate derivative.

19. The implantable medical device according to claim 17, wherein the one or more third peptides comprise an antibody fragment.

20. The implantable medical device according to claim 17, wherein the one or more third proteins comprise an antibody or an affibody.

21. The implantable medical device according to claim 20, wherein the antibody is selected from the group consisting of an anti-elastin, an anti-collagen, an anti-tissue factor, an anti-laminin or any combination thereof.

22. The implantable medical device according to claim 17, wherein the one or more third oligonucleotides comprise an aptamer.

23. The implantable medical device according to claim 16, wherein the nanoparticles further comprise a stealth group operatively coupled to the surface of the nanoparticles.

24. The implantable medical device according to claim 23, wherein the stealth group comprises poly(ethylene glycol), an oligosaccharide, a polysaccharide, poly(vinyl pyrrolidone), gluronic acid or polyacrylamide.

25. A method for treating a vascular disease comprising:

providing an implantable medical device according to claim 1; and

implanting the medical device in a patient in need thereof.

26. The method according to claim 25, wherein the vascular disease is selected from the group consisting of atherosclerosis, restenosis, vulnerable plaque and peripheral arterial disease.