Magnetically-controllable delivery system for therapeutic agents

• US 8,900,293 B2
• Filed: 04/20/2010
• Issued: 12/02/2014
• Est. Priority Date: 04/16/2003
• Status: Active Grant

• Current Assignee: Drexel University
• Original Assignee: Drexel University
• Inventors: Friedman, Gennady, Forbes, Zachary Graham, Yellen, Benjamin Biron, Barbee, Kenneth Andrew
• Primary Examiner(s): PREBILIC, PAUL B
• Application Number:
  US12/763,925
• Publication Number:
  US 20100204674A1
• Time in Patent Office: 1,687 Days
• Field of Search: 424/423, 424/1.29, 623/23.73, 623/18.12, 623/23.57, 623/1.42, 606/907, 604/508, 607/9, 600/12
• US Class Current: 623/1.42
• CPC Class Codes: A61F 2/82 Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents stent-grafts for tubular structures of the body other than blood vessels A61F2/04; stent-grafts for blood vessels A61F2/07; instruments specially adapted for placement or removal of stents or stent-grafts A61F2/95; for closing wounds, or holding wounds closed A61B17/04 - A61B17/115; dilators A61M29/00
• CPC Class Codes: A61F 2210/009 magnetic
• CPC Class Codes: A61L 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 31/022 Metals or alloys
• CPC Class Codes: A61L 31/14 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61M 2037/0007 having means for enhancing the permeation of substances through the epidermis, e.g. using suction or depression, electric or magnetic fields, sound waves or chemical agents
• CPC Class Codes: A61M 37/00 Other apparatus for introducing media into the body for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30; Percutany, i.e. introducing medicines into the body by diffusion through the skin salt baths A61H33/04
• CPC Class Codes: A61N 1/30 Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis
• CPC Class Codes: A61N 2/00 Magnetotherapy

Abstract

A magnetic delivery system for delivering a magnetizable particle to a location in a body, the device includes a magnetizable object implanted in the body, wherein the magnetizable object includes a plurality of segments distributed throughout the magnetizable object and wherein the segments are configured to provide a magnetic gradient for attracting the magnetizable particle and an external source of a magnetic field capable of (i) magnetizing the magnetizable particle and (ii) increasing a degree of magnetization of the magnetizable object and thereby creating the magnetic gradient. A drug delivery system including the magnetic delivery system and a magnetizable particle associated with a therapeutic agent and/or a cell. A cell delivery system based on the magnetic delivery system and a magnetizable particle associated with a cell. A method of using the magnetic delivery system for delivery of a therapeutic agent and/or a cell to a targeted location in a body.

Claims

1. A magnetic delivery system for delivering a magnetizable particle to a location in a body, the magnetic delivery system comprising:

a magnetizable object, wherein the magnetizable object includes a plurality of segments distributed throughout the magnetizable object and wherein the segments are configured to provide a magnetic gradient for attracting the magnetizable particle; and

wherein the segments further comprise a coating wherein the coating is patterned to provide non-uniform magnetization of a surface of the segments when the magnetizable object is magnetized; and

an external source of a magnetic field capable of (i) magnetizing the magnetizable particle and (ii) increasing a degree of magnetization of the magnetizable object and thereby creating the magnetic gradient.

2. The magnetic delivery system of claim 1, wherein a size of each segment is selected to be commensurate with a size of the magnetizable particle such that at least one spatial dimension of each segment does not exceed by more than about 10,000 times at least one spatial dimension of the magnetizable particle.

3. The magnetic delivery system of claim 2, wherein the size of each segment is selected to be commensurate with the size of the magnetizable particle such that at least one spatial dimension of each segment does not exceed by more than about 100 times at least one spatial dimension of the magnetizable particle.

4. The magnetic delivery system of claim 1, wherein the magnetizable object is in the shape of a cylinder, a cylindrical rod, a cube, a cubical rod, a spring, a circular disc, a mesh, a ring, a wire, a sphere or a combination thereof.

5. The magnetic delivery system of claim 1, wherein the magnetizable object is a member selected from the group consisting of a stent, a pacemaker, a catheter, a tube, a vascular graft, an artificial joint, an artificial bone, a prostate seed, an aneurysm coil, a surgical staple, and a suture.

6. The magnetic delivery system of claim 1, wherein the magnetizable object comprises a cluster of gradient forming particles, wherein a surface of each gradient forming particle represents a segment of the magnetizable object.

7. The magnetic delivery system of claim 1, wherein the magnetizable object is made from at least one of materials selected from the group consisting of cobalt, nickel, iron, manganese, samarium and neodymium.

8. The magnetic delivery system of claim 1, wherein the magnetizable object is in a shape of a support made from a metal, a rare earth element, a ceramic, a polymer or a combination thereof.

9. The magnetic delivery system of claim 1, wherein the coating is made from a metal, a rare earth element, a ceramic, a polymer or a combination thereof.

10. The magnetic delivery system of claim 1, wherein the segments comprise patterns of indentations and/or ridges of various length, width, depth and shape.

11. The magnetic delivery system of claim 1, wherein the segments comprise patterns of materials with different degrees of magnetization.

12. The magnetic delivery system of claim 1, further comprising the magnetizable particle.

14. The magnetic delivery system of claim 12, wherein at least one of the magnetizable object and the magnetizable particle is permanently magnetized.

15. The magnetic deliver system of claim 12, wherein the magnetization of at least one of the magnetizable object and the magnetizable particle is increased in the presence of the external magnetic field.

16. The magnetic delivery system of claim 12, wherein the magnetizable particle is in a form of a superparamagnetic colloidal fluid.

17. The magnetic delivery system of claim 12, wherein the magnetizable particle has a diameter of less than 10 micrometers.

18. The magnetic delivery system of claim 12, wherein the magnetizable particle has a diameter from about 10 nm to about 1000 nm.

19. The magnetic delivery system of claim 12, wherein the magnetizable particle has a diameter from 10 nm to 500 nm.

20. The magnetic delivery system of claim 12, wherein the magnetizable particle comprises at least one material selected from the group consisting of Fe₂O₃, Fe₃O₄, FeNi, FePt, Fe, and CoNi alloy.

21. The magnetic delivery system of claim 12, wherein the magnetizable particle comprises a therapeutic agent.

22. The magnetic delivery system of claim 21, wherein the magnetizable particle is in a form of a superparamagnetic colloidal fluid.

23. The magnetic delivery system of claim 12, wherein the magnetizable particle is loaded within a cell, thereby forming a magnetic cell.

24. The magnetic delivery system of claim 23, wherein the magnetic cell comprises a therapeutic agent, such that the therapeutic agent is associated with the cell, the magnetizable particle or both.

25. A method of using the magnetic delivery system of claim 1 for delivery of a therapeutic agent, the method comprising:

providing the external source of the magnetic field;

implanting the magnetizable object in the body, wherein the magnetizable object includes a plurality of segments distributed throughout the magnetizable object and wherein the segments are configured to provide a magnetic gradient for attracting a magnetizable particle comprising a therapeutic agent; and

providing an external magnetic field by initializing the external source and thereby (i) magnetizing the magnetizable particle and (ii) increasing the degree of magnetization the magnetizable object and thereby creating the magnetic gradient for attracting and advancing the magnetizable particle toward the magnetizable object.

26. The method of claim 25, further comprising:

administering the magnetizable particle comprising the therapeutic agent to the body; and

attracting and advancing the magnetizable particle toward the magnetizable object using the magnetic gradient and thereby delivering the therapeutic agent to the location in the body.

27. The method of claim 26, wherein a size of each segment is selected to be commensurate with a size of the magnetizable particle such that at least one spatial dimension of each segment does not exceed by more than about 10,000 times at least one spatial dimension of the magnetizable particle.

28. The method of claim 26, wherein the magnetizable particle is in a form of a superparamagnetic colloidal fluid.

29. The method of claim 26, wherein the magnetizable particle has a diameter from about 10 nm to about 1000 nm.

30. The method of claim 26, wherein the magnetizable particle has a diameter from 10 nm to 500 nm.

31. The method of claim 26, wherein the magnetizable object is a member selected from the group consisting of a stem, a pacemaker, a catheter, a tube, a vascular graft, an artificial joint, an artificial bone, a prostate seed, an aneurysm coil, as surgical staple, and a suture.

32. The method of claim 26, wherein at least one of the magnetizable object and the magnetizable particle is magnetized only in the presence of the external magnetic field.

33. The method of claim 26, wherein at least one of the magnetizable object and the magnetizable particle is permanently magnetized.

34. The method of claim 26, wherein the magnetizable particle comprises a cell such that the magnetizable particle is loaded within a cell and the therapeutic agent is associated with the cell, the magnetizable particle or both.

35. The method of claim 25, wherein implanting the magnetizable object is accomplished by administering a cluster of gradient forming particles wherein a surface of each gradient forming particle represents a segment of the magnetizable object.

36. A method of using the magnetic delivery system of claim 1 for delivery of a cell to a body, the method comprising:

providing the external source of the magnetic field;

implanting the magnetizable object in the body, wherein the magnetizable object includes a plurality of segments distributed throughout the magnetizable object and wherein the segments are configured to provide a magnetic gradient for attracting a magnetizable particle comprising a therapeutic agent;

administering the magnetizable particle loaded within the cell to the body;

providing an external magnetic field by initializing the external source and thereby (i) magnetizing the magnetizable panicle and (ii) increasing the degree of magnetization the magnetizable object and thereby creating the magnetic gradient; and

attracting and advancing the magnetizable particle toward the magnetizable object using the magnetic gradient and thereby delivering the cell to the location in the body.

13. The magnetic delivery system of chum 12, wherein at least one of the magnetizable object and the magnetizable particle is magnetized only in the presence of the external magnetic field.

37. The method of chum 36, wherein a size of each segment is selected to be commensurate with a size of the magnetizable particle such that at least one spatial dimension of each segment does not exceed by more than about 10,000 times at least one spatial dimension of the magnetizable particle.