Particle immobilized coatings and uses thereof

• US 20030129130A1
• Filed: 09/30/2002
• Published: 07/10/2003
• Est. Priority Date: 10/05/2001
• Status: Active Grant

• Current Assignee: Surmodics Incorporated
• Original Assignee: Surmodics Incorporated
• Inventors: Guire, Patrick E., Taton, Kristin S., Wall, John V.
• Granted Patent: US 8,158,106 B2
• Time in Patent Office: Days
• US Class Current: 424/1.11
• CPC Class Codes: A61K 47/6927 the form being a solid microparticle having no hollow or gas-filled cores
• CPC Class Codes: A61K 47/6957 the form being a device or a kit, e.g. stents or microdevices
• CPC Class Codes: A61K 49/0002 General or multifunctional contrast agents, e.g. chelated agents
• CPC Class Codes: A61K 49/1821 coated or functionalised microparticles or nanoparticles
• CPC Class Codes: A61K 51/1244 microparticles or nanoparticles, e.g. polymeric nanoparticles
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/2081 with microcapsules or coated microparticles according to A61K9/50
• CPC Class Codes: A61K 9/5073 having two or more different coatings optionally including drug-containing subcoatings
• CPC Class Codes: A61K 9/5078 with drug-free core
• CPC Class Codes: A61L 2300/44 Radioisotopes, radionuclides
• CPC Class Codes: A61L 2300/604 Biodegradation
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 2300/622 Microcapsules
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 29/18 Materials at least partially X-ray or laser opaque
• CPC Class Codes: A61L 31/18 Materials at least partially X-ray or laser opaque
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

Surface coatings including microparticles immobilized in a matrix of polymeric material on a substrate are described. The microparticles can also include an agent which can be useful for various applications, such as medical applications.

This invention relates to the field of surface coatings for use in various applications. More particularly, the invention relates to surface coating useful for drug delivery, imaging and other uses of microparticles immobilized via a polymeric matrix.

Claims

1. A substrate comprising:

a) a surface;

b) a matrix comprising polymeric material and one or more reactive groups, wherein the matrix is covalently attached to the surface by the reactive groups, and wherein the polymeric material comprises a polymer, copolymer, or combinations thereof; and

c) a plurality of microparticles immobilized in the matrix of polymeric material.

2. The substrate of claim 1 wherein the microparticles have a size in the range of 5 nm to 100 μ

m.

3. The substrate of claim 2 wherein the microparticles have a size in the range of 100 nm to 20 μ

m.

4. The substrate of claim 1 wherein the microparticles comprise a functional agent.

5. The substrate of claim 4 wherein the functional agent is a biologically active agent.

6. The substrate of claim 4 wherein the functional agent is a material detectable by magnetic resonance, ultrasonic imaging, radioisotopic imaging, or photonic imaging.

7. The substrate of claim 1 wherein the microparticles have pores.

8. The substrate of claim 7 wherein the pores range in size from 5 nm to 20 nm.

9. The substrate of claim 1 wherein the microparticles are degradable.

10. The substrate of claim 9 wherein the degradable microparticles comprise a material selected from the group consisting of dextran, poly-lactic acid, poly(lactide-co-glycolide), polycaprolactone, polyphosphazine, polymethylidenemalonate, polyorthoesters, polyhydroxybutyrate, polyalkeneanhydrides, polypeptides, polyanhydrides, and polyesters.

11. The substrate of claim 1 wherein the reactive group is a photoreactive group

12. The substrate of claim 11 wherein the photoreactive group is selected from the group consisting of aryl ketones, arylazides, acyl azides, sulfonyl azides, phosphoryl azides, diazoalkanes, diazoketones, diazoacetates, and ketenes.

13. The substrate of claim 1 wherein the polymer, copolymer, or combinations thereof, is selected from the group consisting of polyacrylamide, polymethacrylamide, polyvinylpyrrolidone, polyacrylic acid, polyethylene glycol, polyvinyl alcohol, and poly(HEMA), copolymers thereof, and combinations thereof.

14. The substrate of claim 1 wherein the microparticles are immobilized in the matrix by entrapment, wherein the entrapment of the microparticles does not depend on the formation of ionic or covalent bonds between the microparticles and the polymeric material.

15. The substrate of claim 1 wherein the matrix has a thickness and the microparticles have a diameter and the thickness of the layer is greater than the diameter of the microparticles.

16. The substrate of claim 1 wherein a plurality of compounds smaller than the microparticles are diffusible in the matrix of polymeric material.

17. The substrate of claim 1 wherein the surface comprises a surface of a medical device.

18. The substrate of claim 1 wherein the matrix comprises a polymer crosslinking compound.

19. The substrate of claim 18 wherein the polymer crosslinking compound comprises at least one photoactivatable group.

20. A kit for coating the surface of a substrate with a plurality of microparticles immobilized in a matrix of polymeric material, the kit comprising:

a) at least one set of microparticles;

b) a matrix-forming material comprising polymeric material and one or more reactive groups, wherein the polymeric material comprises a polymer, copolymer, or combinations thereof, and wherein the matrix-forming material is configured and arranged to be covalently attached to the surface of a substrate via the one or more reactive groups and able to immobilize the microparticles on the surface of the substrate; and

c) instructions for preparing a coated surface.

21. The kit of claim 20, wherein the at least one reactive group is a photoreactive group.

22. The kit of claim 20, wherein the at least one set of microparticles is configured and arranged to be coupled to a functional agent.

23. The kit of claim 20, wherein the at least one set of microparticles comprises a functional agent.

24. The kit of claim 23, wherein the functional agent is a biologically active agent.

25. The kit of claim 20 wherein the functional agent is a material detectable by magnetic resonance, ultrasonic imaging, radioisotopic imaging, or photonic imaging.

26. The kit of claim 20 wherein the matrix-forming material comprises a polymer crosslinking compound.

27. A method for coating a surface of a substrate, the method comprising steps of:

a) preparing a mixture comprising i) a plurality of microparticles and ii) a matrix-forming material comprising a polymeric material and at least one reactive group, wherein the polymeric material comprises a polymer, copolymer, or combinations thereof;

b) disposing the mixture on the surface of the substrate; and

c) treating the mixture to activate the reactive group thereby forming a matrix wherein the polymer, copolymer, or combinations thereof, are attached to the surface of the substrate, and wherein the microparticles become immobilized within the matrix on the substrate.

28. The method of claim 27, wherein the at least one reactive group is a photoreactive group, and in the step of treating the photoreactive group is activated by electromagnetic energy.

29. The method of claim 27 where, in the step of preparing, the polymer, copolymer, or combinations thereof, is selected from the group consisting of polyacrylamide, polymethacrylamide, polyvinylpyrrolidone, polyacrylic acid, polyethylene glycol, polyvinyl alcohol, and poly(HEMA), copolymers thereof, and combinations thereof.

30. The method of claim 27 where, in the step of treating, the microparticles become entrapped in the matrix, wherein the entrapment of the microparticles does not depend on the formation of ionic or covalent bonds between the microparticles and the polymeric material.

31. The method of claim 27 where, in the step of preparing, the plurality of microparticles comprise at least two sets of microparticles, wherein a first set of microparticles comprise a first functional agent and wherein a second set of microparticles comprise a second functional agent, and wherein the first functional agent and second functional agent are otherwise mutually incompatible in a certain environment.

32. The method of claim 31 where the first functional agent is more hydrophobic than the second functional agent and both first and second functional agents are biologically active agents.

33. The method of claim 27 where, in the step of preparing, the plurality of microparticles comprise at least two sets of microparticles, wherein a first set of microparticles comprise a first functional agent and wherein a second set of microparticles comprise a second functional agent, and wherein the first functional agent and second functional agent are released at different rates from the first set of microparticles and the second set of microparticles, respectively.

34. A method for administering at least one biologically active agent to a subject comprising the steps of:

a) providing a device having a surface and a matrix covalently attached to the surface, wherein the matrix comprises a polymeric material and at least one reactive group, wherein the matrix is covalently attached to the surface by the at least one reactive group, wherein the polymeric material comprises a polymer, copolymer, or combinations thereof, wherein a plurality of microparticles are immobilized in the matrix, and wherein the microparticles comprise at least one biologically active agent; and

b) placing the device in a subject or delivering the device to a subject, wherein the biologically active agent becomes available to the subject.

35. The method of claim 34 wherein the microparticles are degradable and have incorporated the biologically active agent.

36. The method of claim 35 where, in the step of placing, the biologically active agent becomes available to the subject upon degradation of the microparticle.

37. The method of claim 34 where, in the step of providing, the plurality of microparticles comprise at least two sets of microparticles, wherein a first set of microparticles comprise a first functional agent and wherein a second set of microparticles comprise a second functional agent, and wherein the first functional agent and second functional agent are otherwise mutually incompatible in a certain environment.

38. The method of claim 34 where, in the step of providing, the plurality of microparticles comprise at least two sets of microparticles, wherein a first set of microparticles comprise a first functional agent and wherein a second set of microparticles comprise a second functional agent, and wherein the first functional agent and second functional agent are released at different rates from the first set of microparticles and the second set of microparticles, respectively.

39. A method for detecting a device comprising the steps of:

a) providing a device having a surface and a matrix covalently attached to the surface, wherein the matrix comprises a polymeric material and at least one reactive group, wherein the matrix is covalently attached to the surface by the at least one reactive group, wherein the polymeric material comprises a polymer, copolymer, or combinations thereof, and wherein a plurality of microparticles are immobilized in the matrix, wherein the microparticles are detectable by magnetic resonance, ultrasonic imaging, radioisotopic imaging, photonic imaging, or combinations thereof; and

b) placing the device in subject or an object; and

c) detecting the device.

40. The method of claim 39 wherein the microspheres comprise a paramagnetic material and the step of detecting comprises utilizing magnetic resonance imaging.

41. The method of claim 39 wherein the microspheres comprise a vapor phase chemical and the step of detecting comprises utilizing ultrasonic imaging.

42. The method of claim 39 wherein the microspheres comprise a radioactive material having a radioactive emission and the step of detecting comprises detecting the radioactive emission.

43. The method of claim 39 wherein the device is at least a portion of a medical device.

44. The method of claim 39 wherein the plurality of microparticles comprises at least two sets of microparticles and each set has a different detectable property.

45. A cell-reactive surface comprising:

a) a surface;

b) a matrix comprising polymeric material and a reactive group, wherein the polymeric material comprises a polymer, copolymer, or combinations thereof, and wherein the reactive group covalently attaches the matrix to the surface; and

c) a plurality of microparticles immobilized in the matrix arranged to provide a topography for cell interaction.

46. The cell-reactive surface of claim 45 wherein the plurality of microparticles immobilized in the matrix of polymeric material promotes or inhibits the attachment of cells to the surface.

47. The cell-reactive surface of claim 45 wherein the plurality of microparticles immobilized in the matrix of polymeric material allows for cell adhesion and growth.

48. The cell-reactive surface of claim 45 wherein the microparticles are coupled to a molecule reactive with cell surface proteins.

49. The cell-reactive surface of claim 45 wherein the surface comprises a portion of a medical device.

50. The cell reactive surface of claim 45 wherein the surface comprises a portion of a cell culture device.