Magnetic particle-based therapy

• US 20060025713A1
• Filed: 05/12/2004
• Published: 02/02/2006
• Est. Priority Date: 05/12/2003
• Status: Abandoned Application

• Current Assignee: United States Department of Energy
• Original Assignee: United States Department of Energy
• Inventors: Kaminski, Michael D., Rosengart, Alex
• Application Number:
  US10/844,180
• Publication Number:
  US 20060025713A1
• Time in Patent Office: Days
• US Class Current: 604/5.20
• CPC Class Codes: A61K 41/00 Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
• CPC Class Codes: A61K 9/0009 involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis microelectromechanical systems A61K9/0097
• CPC Class Codes: A61K 9/5094 Microcapsules containing magnetic carrier material, e.g. ferrite for drug targeting
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention provides materials and methods for the administration of an effectively magnetic medication or diagnostic reagent, or for the removal, sequestration, or effective conversion to a non-deleterious condition of a deleterious substance such as a toxin (e.g., biological, chemical, or radiological compound or composition) in vivo by administering a biocompatible magnetic particle to an organism in need, e.g., by delivery to the bloodstream, with the organism optionally having an internal magnetizable stent or magnetizable seed. The materials and methods are useful in the diagnosis and treatment of a variety of acute and chronic diseases, disorders and conditions afflicting man and other organisms, as well as for the removal of a variety of deleterious substances, including toxins, with the optional aid of an external magnetic generator and an optional magnetic filtration device.

Claims

1. A method for controlling the administration of an effectively magnetized compound selected from the group consisting of a medication, a diagnostic agent, a specific binding partner for a deleterious substance and an inhibitor of a deleterious substance comprising:

(a) introducing a magnetizable device selected from the group consisting of a magnetizable stent and a magnetizable seed into an organism in need, wherein said device is magnetically associated with said compound; and

(b) establishing a magnetic field across said device, thereby capturing said compound.

2. The method according to claim 1 wherein said compound is effectively magnetized by attachment to a biocompatible magnetic particle comprising a mean diameter between 100 and 5,000 nanometers and exhibiting an in vivo half-life of at least fifteen minutes.

3. The method according to claim 2 wherein establishing a magnetic field comprises application of an external magnetic field across said device.

4. The method according to claim 2 wherein said device is introduced into an organism in need by a procedure selected from the group consisting of surgical implantation, catheter-mediated implantation, cannula-mediated implantation and stereotactic placement.

5. The method according to claim 2 wherein said compound is a medication selected from the group consisting of a chemotherapeutic, a radioactive isotope, a fibrinolytic agent and an anti-platelet aggregation drug.

6. The method according to claim 2 wherein said compound is a specific binding partner for a deleterious substance selected from the group consisting of a specific anti-deleterious substance antibody, a fragment of an anti-deleterious substance antibody specifically binding said deleterious substance and a radioisotope chelator.

7. The method according to claim 2 wherein said magnetic particle comprises a magnetizable material selected from the group consisting of magnetite (Fe₃O₄), maghemite (g-Fe₂O₃), metallic iron, cobalt, nickel, permalloy, cobalt ferrite (CoFe₂O₄), NdFeB, SmFe₂, TbFe₂, TbDyFe, NdCo₅, SmCo₅, LaCo₅, CeCo₅ and PrCo₅.

8. The method according to claim 2 wherein said magnetic particle is coated with a biocompatible polymer selected from the group consisting of poly (lactic co-glycolic acid), poly (lactic acid), a linear polyethylene glycol, a branched polyethylene glycol, a propylene glycol, dextran and albumin.

9. A method for controlling the administration of an effectively magnetized compound selected from the group consisting of a medication, a diagnostic agent, a specific binding partner for a deleterious substance and an inhibitor of a deleterious substance comprising:

(a) introducing a magnetizable device selected from the group consisting of a magnetizable stent and a magnetizable seed into an organism in need, wherein said device is associated with said compound;

(b) administering a therapeutically effective amount of an effectively magnetizable compound to said organism; and

(c) establishing a magnetic field across said device, thereby capturing said compound.

10. The method according to claim 9 wherein said compound is effectively magnetized by attachment to a biocompatible magnetic particle comprising a mean diameter between 100 and 5,000 nanometers and exhibiting an in vivo half-life of at least fifteen minutes.

11. The method according to claim 10 wherein said administering is accomplished by a procedure selected from the group consisting of intraarterial injection, intravenous injection, intramuscular injection, intraperitoneal injection, subcutaneous injection, transdermal delivery, inhalation, intraluminal spraying and topical administration.

12. The method according to any one of claims 2 or 10 wherein said compound is selected from the group consisting of a specific binding partner for a deleterious substance and an inhibitor of a deleterious substance, said method further comprising removal of said compound attached to said magnetic particle after a time period sufficient for said compound to bind to said deleterious substance, thereby removing said deleterious substance.

13. The use of a magnetic particle according to any one of claims 2 or 10 attached to a medication in the preparation of a medicament for the treatment of a disease, disorder or condition in an organism in need.

14. The use of a magnetic particle according to any one of claims 2 or 10 attached to a diagnostic agent in the preparation of a medicament for the diagnosis of a disease, disorder or condition in an organism in need.

15. A kit comprising a compound attached to a magnetic particle according to any one of claims 2 or 10 and a set of instructions for administration of said compound to treat or diagnose a disease in an organism in need.

16. A method for removing a deleterious substance from an organism comprising:

(a) administering a biocompatible magnetic particle to an organism under conditions wherein said particle binds to said substance, and wherein said particle has an in vivo half-life of at least thirty minutes; and

(b) removing said particle from said organism by exposing said particle to a magnetic field, thereby removing said deleterious substance.

17. The method according to claim 16 wherein said particle specifically binds said deleterious substance.

18. The method according to claim 17 wherein said particle has a diameter between about 100 and 5,000 nanometers and exhibits an in vivo half life of at least 15 minutes.

19. The method according to claim 18 wherein said deleterious substance is selected from the group consisting of a bacterial cell, a virus, a DNA, a RNA, a prion, a radionuclide, a radioactive material and a metal.

20. The method according to claim 16 wherein said deleterious substance is a toxin.

21. The method according to claim 20 wherein said toxin is selected from the group consisting of Abrin, Adenylate cyclase, Aerolysin, Aflatoxin, Alpha toxin, Adroctonin, Anthrax toxin, Botulinum toxin (A), Botulinum toxin (B), Botulinum toxin (C), Botulinum toxin (D), Botulinum toxin (E), Botulinum toxin (F), Botulinum toxin (G), C2 toxin, C3 toxin, Cholera enterotoxin CLDT, CFN, Conotoxin-alpha, Conotoxin-alpha-A, Conotoxin-psi, Conotoxin-omega, Conotoxin-mu, Conotoxin-delta, Conotoxin-kappa, Cytotoxic necrotizing factor type I, oxynivalenol, Dermonecrotic toxin, Diacetoxyscirpenol, Diptheria toxin, EAST, Epsilon toxin, Equinatoxin II, Erythrogenic toxin, Exfoliatin toxin, Exotoxin A, Flavocetin, Hemolysin, Huwentoxin-I, Huwentoxin-II, Huwentoxin-UV, Iota toxin, Leukocydin F, Listeriorlysin O, LT toxin, Mastoparan, Nivalenol, Nodularin, Perfringolysin O, Perfringens enterotoxin, Pertussis toxin, Pneumolysin, Pyrogenic exotoxin, Ricin, Saxitosin, Scorpion toxin, Shiga, ST toxin, Staphylococcus enterotoxin, Streptolysin O, T-2 toxin, Tetanus toxin, Tetradotoxin, Toxic shock syndrome toxin, Toxin A, Toxin B and a radionuclide.

22. The method according to claim 21 wherein said toxin is selected from the group consisting of Anthrax toxin, Botulinum toxin (A), Botulinum toxin (B), Botulinum toxin (C), Botulinum toxin (D), Botulinum toxin (E), Botulinum toxin (F), Botulinum toxin (G), Ricin, Saxitosin, Staphylococcus enterotoxin, and Tetradotoxin.

23. The method according to claim 20 wherein said toxin is selected from the group consisting of americium-241, plutonium-239, plutonium-240, plutonium-238, uranium-238, uranium-235, europium-154, europium-155, cesium-137, strontium-90, iodine-131, iodine-125, iodine-129, technetium-99, neptunium-237, curium-244, rhenium-188, radium-228, radium-226 and cobalt-60.

24. The method according to claim 16 wherein said particle has a paramagnetic core.

25. The method according to claim 24 wherein said core is encased in a compound selected from the group consisting of polystyrene, poly (lactic acid) and poly (lactic-glycolic acid).

26. The method according to claim 16 wherein said particle is effectively coated with a polyalkylene glycol.

27. The method according to claim 26 wherein said compound is selected from the group consisting of polyethylene glycol and polypropylene glycol.

28. The method according to claim 16 wherein said particle further comprises a specific binding partner for said substance.

29. The method according to claim 28 wherein said binding partner is selected from the group consisting of a receptor specific for a ligand, a ligand specific for a receptor, a ligand specific for a radionuclide, an antigen, a hapten and an antibody.

30. The method according to claim 16 wherein said organism is selected from the group consisting of a multicellular plant, a fish, an amphibian, a reptile and a mammal.

31. The method according to claim 16 wherein said organism is a human.

32. The method according to claim 16 wherein said administering is selected from the group consisting of injection, surgical implantation, catheterization, cannulation, oral delivery, anal delivery and topical delivery.

33. The method according to claim 32 wherein said administering is continuous.

34. The method according to claim 16 wherein removing said particle is achieved by removing said particle from a biological fluid.

35. The method according to claim 34 wherein said biological fluid is selected from the group consisting of blood, plasma and lymph.

36. The method according to claim 35 wherein said biological fluid is blood.

37. The method according to claim 16 wherein said removing is achieved using a magnetic field gradient.

38. The method according to claim 37 wherein said magnetic field is an electromagnetic field.

39. The method according to claim 37 wherein the step of removing comprises:

(a) circulating blood through a closed-loop catheter system in fluid communication with the bloodstream of said organism;

(b) exposing the blood to a pre-defined magnetic field gradient, thereby impeding the flow of said particle in said blood; and

(c) returning the blood to said organism.

40. The method according to claim 16 wherein the substance is an endogenous substance.

43. A kit comprising a compound attached to a magnetic particle according to any one of claims 16, 41 or 42 and a set of instructions for administration of said compound to treat or diagnose a disease in an organism in need.

41. A method for decreasing the deleterious activity of a substance in an organism by modulating the activity of said substance, comprising administering a biocompatible magnetic particle to an organism under conditions wherein said particle binds to said substance, wherein said particle has an in vivo half-life of at least thirty minutes, and wherein said bound substance exhibits detectably decreased deleterious activity, thereby decreasing the deleterious activity of said substance.

42. A method of diagnosing a deleterious substance-induced condition in an organism comprising:

(a) administering a biocompatible magnetic particle to an organism under conditions wherein said particle binds to said substance, and wherein said particle has an in vivo half-life of at least fifteen minutes;

(b) removing said particle from said organism by exposing said particle to a magnetic field; and

(c) identifying said deleterious substance, thereby diagnosing said condition.