Nanoshells on polymers

• US 8,017,237 B2
• Filed: 06/23/2006
• Issued: 09/13/2011
• Est. Priority Date: 06/23/2006
• Status: Expired due to Fees

• Current Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories Incorporated)
• Original Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories Incorporated)
• Inventors: Ludwig, Florian Niklas, Davalian, Dariush, Pacetti, Stephen D., Hossainy, Syed F. A.
• Primary Examiner(s): KILIMAN, LESZEK B
• Application Number:
  US11/473,822
• Publication Number:
  US 20070298257A1
• Time in Patent Office: 1,908 Days
• Field of Search: 428/403, 428/407, 427/212, 424/46
• US Class Current: 428/403
• CPC Class Codes: A61K 38/446 Superoxide dismutase (1.15)
• CPC Class Codes: A61K 41/0052 Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
• CPC Class Codes: A61K 47/6923 the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb
• CPC Class Codes: A61K 47/6925 the form being a microcapsule, nanocapsule, microbubble or nanobubble
• CPC Class Codes: A61K 47/6929 the form being a nanoparticle, e.g. an immuno-nanoparticle
• CPC Class Codes: A61K 47/6931 the material constituting the nanoparticle being a polymer
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/5031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/5115 Inorganic compounds
• CPC Class Codes: A61K 9/5138 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61L 2300/00 Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
• CPC Class Codes: A61L 2400/06 Flowable or injectable implant compositions
• CPC Class Codes: A61L 2400/12 Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• 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: B01J 13/02 : Making microcapsules or microballoons for medical preparations A61K9/50
• CPC Class Codes: B22F 1/18 : Non-metallic particles coated with metal
• CPC Class Codes: B82Y 5/00 : Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: Y10S 977/773 : Nanoparticle, i.e. structure having three dimensions of 100 nm or less
• CPC Class Codes: Y10S 977/906 : Drug delivery
• CPC Class Codes: Y10T 428/2991 : Coated
• CPC Class Codes: Y10T 428/2998 : including synthetic resin or polymer

Abstract

Nano-constructs comprising nanoshells and methods of using the nano-constructs for treating or ameliorating a medical condition are provided.

Claims

1. A nano-construct comprising:

(a) a core material comprising a polymer,

(b) a nanoshell formed on the core material, and

(c) a bioactive agent,

wherein the polymer is a degradable polymer selected from the group consisting of a polyester, poly(ester amide), polyether, polyanhydride, polyorthoester or a non-degradable polymer selected from the group consisting of poly(N-(3-aminopropyl)methacrylamide), a copolymer of N-(3-aminopropyl)methacrylamide, and a combination of these, and

wherein the nanoshell comprises a metal having a thickness from about 5 nm to about 50 nm selected from the group consisting of gold, iron, magnesium, zinc, calcium, tungsten, alloys based on these metals, and combinations thereof.

2. The nano-construct of claim 1 wherein the nanoshell comprises gold.

3. The nano-construct of claim 2 wherein the gold nanoshell has a thickness between about 5 nm and about 25 nm.

4. The nano-construct of claim 1 wherein the core material has a size in the range between about 150 nm to about 2000 nm.

5. The nano-construct of claim 1 wherein the nanoshell on the core material is porous to the bioactive agent.

6. The nano-construct of claim 1 wherein the nanoshell comprises iron, magnesium, zinc, calcium, tungsten, alloys based on these metals, or combinations thereof.

7. The nano-construct of claim 1 wherein the nanoshell comprises an electrically conductive, organic material.

8. The nano-construct of claim 1 wherein the nanoshell comprises graphite or a conductive polymer.

9. The nano-construct of claim 1 wherein the nanoshell comprises poly(L-lactide), polyhydroxyalkanoate, polycaprolactone, or combinations thereof.

10. The nano-construct of claim 1 further comprising a substrate that includes the bioactive agent.

11. The nano-construct of claim 10 wherein the substrate is a small unilamellar vesicle (SUV) encapsulating the bioactive agent.

12. The nano-construct of claim 10 wherein the substrate is a liposome, polymersome, or hybrid vesicle.

13. The nano-construct of the claim 1 wherein the core material further comprises ferromagnetic or magnetic ceramic particles.

14. The nano-construct of claim 1 wherein the core material comprises a peptide, a protein, or a combination of these.

15. The nano-construct of claim 1 further comprising a targeting molecule on the surface of the nano-construct.

16. The nano-construct of claim 15 wherein the targeting molecule is a surface-conjugated ligand for receptors on an inflamed endothelium.

17. The nano-construct of claim 1 in a formulation suitable for systemic delivery or local delivery into a human being.

18. The nano-construct of claim 17 wherein the systemic delivery is injection.

19. The nano-construct of claim 17 wherein the local delivery is delivery by a device comprising a catheter.

20. The nano-construct of claim 1 wherein the bioactive agent is selected from the group consisting of paclitaxel, docetaxel, estradiol, 17-beta-estradiol, nitric oxide donors, super oxide dismutases, super oxide dismutase mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), tacrolimus, dexamethasone, rapamycin, rapamycin derivatives, 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, 40-O-tetrazole-rapamycin, 40-epi-(N-1-tetrazolyl)-rapamycin (ABT-578), γ

-hirudin clobetasol, pimecrolimus, imatinib mesylate, midostaurin, prodrugs thereof, co-drugs thereof, and combinations of these.

36. A method of treating, preventing, or ameliorating a medical condition, comprising:

delivering to a disease site in the body of a human being in need of treatment the nano-construct of claim 1,

wherein the nano-construct releases the bioactive agent.

37. The method of claim 36 wherein the bioactive agent is released by radiating the nano-construct with radiation, and

wherein the nano-construct converts the radiation into heat.

38. The method of claim 37 wherein the radiation uses a near infrared (NIR) electromagnetic radiation transmitted through a catheter-based fiber-optic.

39. The method of claim 37 wherein the radiation is electromagnetic and is applied outside the body of the subject.

40. The method of claim 36 wherein the delivering comprises allowing the nano-construct to extravasate through leaky vasculature in the target tissue.

41. The method of claim 36 wherein the nano-construct comprises targeting molecules on the surface of the nano-construct.

42. The method of claim 41 wherein the targeting molecules comprises surface-conjugated ligands for receptors on an inflamed endothelium.

43. The method of claim 36 wherein the nano-construct comprises a surface-disguising compound on the surface of the nano-construct that increases the circulation time of the nano-construct.

44. The method of claim 43 wherein the surface-disguising compound comprises poly(ethylene glycol).

45. The method of claim 36 wherein medical condition is one or more of atherosclerosis, tumor, a nephrosis, vulnerable plaque, diffuse atherosclerotic disease, diabetic retinopathy, aneurysm, anastomotic hyperplasia, claudication, chronic total occlusion, dysfunctional endothelium, recurring thrombus, or fibrin accumulation.

46. The method of claim 36 wherein the bioactive agent is selected from the group consisting of paclitaxel, docetaxel, estradiol, 17-beta-estradiol, nitric oxide donors, super oxide dismutases, super oxide dismutase mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), tacrolimus, dexamethasone, rapamycin, rapamycin derivatives, 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, 40-O-tetrazole-rapamycin, 40-epi-(N-1-tetrazolyl)-rapamycin (ABT-578), γ

-hirudin, clobetasol, pimecrolimus, imatinib mesylate, midostaurin, prodrugs thereof, co-drugs thereof, and combinations of these.

21. A method of forming a nano-construct, comprising:

forming a nanoshell on a core material comprising a polymer, and incorporating at least one bioactive agent with the nanoshell or the core material, wherein the polymer is a degradable polymer or a non-degradable polymer, the non-degradable polymer is selected from the group consisting of poly(N-(3-aminopropyl)methacrylamide), a copolymer of N-(3-aminopropyl)methacrylamide, and a combination of these; and

wherein the nanoshell comprises a metal having a thickness from about 5 nm to about 50 nm selected from the group consisting of gold, iron, magnesium, zinc, calcium, tungsten, alloys based on these metals, and combinations thereof.

22. The method of claim 21 wherein the core material encapsulates at least one bioactive agent.

23. The method of claim 21 wherein the nanoshell is porous.

24. The method of claim 21 further comprising connecting the nano-construct to a substrate.

25. The method of claim 24 wherein the substrate comprises a self-assembled structure.

26. The method of claim 21 wherein the nanoshell comprises gold and has a thickness between about 5 nm and about 25 nm.

27. The method of claim 21 wherein the nanoshell consists essentially of gold and has a thickness between about 5 nm and about 25 nm.

28. The method of claim 21 wherein the core material has a size between about 150 nm and about 2000 nm.

29. The method of claim 21 wherein the core material comprises a peptide, a protein, or a combination of these.

30. The method of claim 21 wherein the nano-construct comprises a targeting molecule on the surface of the nano-construct.

31. The method of claim 29 wherein the targeting molecule is a surface-conjugated ligand for receptors on an inflamed endothelium.

32. The method of claim 21 wherein the nano-construct is in a formulation suitable for systemic delivery or local delivery into a human being.

33. The method of claim 32 wherein the systemic delivery is injection.

34. The method of claim 32 wherein the local delivery is delivery by a device comprising a catheter.

35. The method of claim 21 wherein the bioactive agent is selected from the group consisting of paclitaxel, docetaxel, estradiol, 17-beta-estradiol, nitric oxide donors, super oxide dismutases, super oxide dismutase mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), tacrolimus, dexamethasone, rapamycin, rapamycin derivatives, 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, 40-O-tetrazole-rapamycin, 40-epi-(N-1-tetrazolyl)-rapamycin (ABT-578), γ

-hirudin, clobetasol, pimecrolimus, imatinib mesylate, midostaurin, prodrugs thereof, co-drugs thereof, and combinations of these.