Nanoshells on polymers

• US 8,592,036 B2
• Filed: 09/20/2012
• Issued: 11/26/2013
• 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: Pacetti, Stephen D., Hossainy, Syed F. A., Davalian, Dariush, Ludwig, Florian Niklas
• Primary Examiner(s): KILIMAN, LESZEK B
• Application Number:
  US13/623,818
• Publication Number:
  US 20130018299A1
• Time in Patent Office: 432 Days
• Field of Search: 428/403, 428/407, 424/46, 427/212
• 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 around the core material, and

(c) optionally a bioactive agent,

wherein the polymer is a degradable polymer or a non-degradable polymer, wherein the degradable polymer is selected from the group consisting of a polyester, poly(ester amide), polyether, polyanhydride, polyorthoester, and combinations thereof, and

wherein the nanoshell comprises an electrically conductive material.

2. The nano-construct of claim 1, wherein the electrically conductive material comprises an electrically conductive, organic material, graphite, or a conductive polymer.

3. The nano-construct of claim 1, wherein the nanoshell comprises a metal selected from the group consisting of gold, iron, iron based alloys, magnesium, magnesium alloys, zinc, calcium, tungsten, alloys based on these metals, and combinations thereof.

4. The nano-construct of claim 1, wherein the nanoshell further comprises poly(L-lactide), polyhydroxyalkanoate, polycaprolactone, or a combination thereof.

5. The nano-construct of claim 1, wherein the nanoshell has a thickness between about 5 and about 25 nm.

6. The nano-construct of claim 1, wherein the nanoshell surrounding the core material is porous to the optional bioactive agent, and wherein the optional bioactive agent is present, and is selected from the group consisting of paclitaxel, docetaxel, estradiol, 17-beta-estradiol, nitric oxide donors, super oxide dismutases, 4 amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), tacrolimus, dexamethasone, rapamycin, 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-(N1-tetrazolyl)-rapamycin (ABT-578), γ

-hiridun, clobetasol, pimecrolimus, imatinib mesylate, midostaurin, and combinations thereof.

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

8. The nano-construct of claim 1, wherein the core material further comprises ferromagnetic or magnetic ceramic particles, a peptide, a protein, or a combination thereof.

9. The nano-construct of claim 1, further comprising:

a substrate selected from the group consisting of a small unilamellar vesicle (SUV), a liposome, a polymersome, and a hybrid vesicle.

10. The nano-construct of claim 1, further comprising:

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

20. A method of treating, 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 6, and

causing the nano-construct to release the bioactive agent.

21. The method of claim 20, wherein the causing comprises:

irradiating the nano-construct,

wherein the nano-construct converts the radiation into heat.

22. The method of claim 21, wherein irradiating the nano-construct comprises transmitting a near infrared (NIR) electromagnetic radiation through a catheter-based fiber-optic.

23. The method of claim 21, wherein irradiating the nano-construct comprises applying electromagnetic radiation outside the body of the subject.

24. The method of claim 20, wherein the delivering comprises:

allowing the nano-constructs to extravasate through leaky vasculature in the target tissue.

25. The method of claim 20, wherein the nano-construct comprises a targeting molecule on the surface of the nano-construct.

26. The method of claim 25, wherein the targeting molecule comprises surface-conjugated ligands against receptors on an inflamed endothelium.

27. The method of claim 20, 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.

28. The method of claim 27, wherein the surface-disguising compound comprises poly(ethylene glycol).

29. The method of claim 20, wherein medical condition is one or more from the group including atherosclerosis, tumor, a nephrosis, vulnerable plaque, diffuse atherosclerotic disease, diabetic retinopathy, aneurysm, anastomotic hyperplasia, claudication, chronic total occlusion, dysfunctional endothelium, recurring thrombus, and fibrin accumulation.

11. A method comprising:

forming a nanoshell around a polymeric core material,

wherein the polymer is a degradable polymer or a non-degradable polymer, wherein the degradable polymer is selected from the group consisting of a polyester, poly(ester amide), polyether, polyanhydride, polyorthoester, and combinations thereof, and

wherein the nanoshell comprises an electrically conductive material.

12. The method of claim 11, further comprising:

connecting the nano-construct to a substrate.

13. The method of claim 12, wherein the substrate comprises a self-assembled structure.

14. The method of claim 11, wherein the core material encapsulates at least one bioactive agent, and wherein the at least one bioactive agent is selected from the group consisting of paclitaxel, docetaxel, estradiol, 17-beta-estradiol, nitric oxide donors, super oxide dismutases, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), tacrolimus, dexamethasone, rapamycin, 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-(N1-tetrazolyl)-rapamycin (ABT-578), γ

-hirudin, clobetasol, pimecrolimus, imatinib mesylate, midostaurin, and combinations thereof.

15. The method of claim 11, wherein the core material comprises a peptide, a protein, or a combination thereof.

16. The method of claim 11, wherein the core material has a size between about 150 nm and about 200 nm.

17. The method of claim 11, wherein the nanoshell is porous.

18. The method of claim 11, wherein the nanoshell comprises gold and has a thickness between about 5 and about 25 nm.

19. The method of claim 12, wherein the nano-construct comprises a targeting molecule on the surface of the nano-construct, and wherein the targeting molecule is a surface-conjugated ligand against receptors on an inflamed endothelium.