Particle immobilized coatings and uses thereof
View Patent ↗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.
1. A method for administering a biologically active agent to a subject comprising the steps of:
a) providing an implantable medical device comprising a coating on a surface of the device, the coating comprising
(i) a matrix of polymeric material, the matrix comprising a hydrophobic polymeric matrix material and photoreactive groups activated to covalently bond to a target chemical structure, and
(ii) a plurality of microparticles immobilized in the matrix of polymeric material, wherein the microparticles comprise a biologically active agent, and the microparticles are at least 100 nm in diameter; and
b) placing the device in a subject or delivering the device to a subject, wherein the matrix and microparticles are in contact with a fluid-containing environment, wherein the fluid causes release of the biologically active agent from the microparticles, wherein the matrix allows the diffusion of molecules in and out of the matrix, and wherein the biologically active agent is released from the matrix and becomes available to the subject.
2. The method of claim 1 wherein the biologically active agent comprises a hydrophilic compound.
3. The method of claim 1 which is performed for the treatment of a cardiovascular disease wherein the biologically active agent is useful for treating the cardiovascular disease.
4. The method of claim 1 wherein the microparticles have a size in the range of 100 nm to 9.9 μm.
5. The method of claim 4 wherein the microparticles have a size in the range of 100 nm to 5 μm.
6. The method of claim 1 wherein a majority of the bioactive agent present in the coating is not released until a time point of six hours or later from the time of placing the device in a subject or delivering the device to a subject.
7. The method of claim 1 wherein the microparticles have a size in the range of 100 nm to 20 μm.
8. The method of claim 1 wherein the microparticles have pores.
9. The method of claim 8 wherein the pores range in size from 5 nm to 20 nm.
10. The method of claim 1 wherein the microparticles are degradable.
11. The method of claim 10 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.
12. The method of claim 1 wherein the matrix is covalently attached to the surface by reactive groups, and the reactive groups comprise photoreactive groups.
13. The method of claim 12 wherein the photoreactive groups are selected from the group consisting of aryl ketones, arylazides, acyl azides, sulfonyl azides, phosphoryl azides, diazoalkanes, diazoketones, diazoacetates, and ketenes.
14. The method of claim 1 wherein the polymeric material is selected from the group consisting of polyacrylamide, polymethacrylamide, polyvinylpyrrolidone, polyacrylic acid, polyethylene glycol, polyvinyl alcohol, and poly(HEMA), copolymers thereof, and combinations thereof.
15. The method 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.
16. The method 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.
17. The method of claim 1 wherein the matrix comprises a polymer crosslinking compound.
18. The method of claim 17 wherein the polymer crosslinking compound comprises at least one photoactivatable group.
19. The method of claim 1 wherein the hydrophobic polymeric matrix material is selected from the group consisting of polystyrene, polymethylmethacrylate (PMMA), polybutylmethacrylate (PBMA), and polyurethanes.
20. The method of claim 1 wherein the coating comprises a polysaccharide.
21. The method of claim 1 wherein the matrix allows the immobilization of microparticles that are at least 100 nm diameter and allows the diffusion of molecules that are 50 nm or less in and out of the polymeric matrix.
22. The method of claim 1 wherein the matrix allows the immobilization of microparticles that are at least 100 nm diameter and allows the diffusion of molecules that are 25 nm or less, in and out of the polymeric matrix.
23. The method of claim 2 wherein the biologically active hydrophilic compound comprises a protein.
24. The method of claim 2 wherein the biologically active hydrophilic compound comprises an antiproliferative agent.
25. The method of claim 2 wherein the microparticles further comprise an outer coating comprising poly(ethyleneglycol) (PEG).
26. A method for administering a biologically active agent to a subject comprising the steps of:
a) providing an implantable medical device comprising a coating on a surface of the device, the coating comprising
(i) a matrix of polymeric material comprising a hydrophobic polymer and
(ii) a plurality of microparticles immobilized in the matrix of polymeric material, wherein the microparticles comprise a biologically active agent, and the microparticles have a size in the range of 100 nm to 9.9 μm in diameter; and
b) placing the device in a subject or delivering the device to a subject, wherein the matrix and microparticles are in contact with a fluid-containing environment, wherein the fluid causes release of the biologically active agent from the microparticles, wherein the matrix allows the diffusion of molecules in and out of the matrix, and wherein the biologically active agent is released from the matrix and becomes available to the subject.
27. The method of claim 26 wherein the microparticles have a size in the range of 100 nm to 5 μm.