Drug delivery platform
View Patent ↗A stent based drug delivery system. A biological agent of interest is entrapped within a matrix, which is loaded into channels on the surface of a stent. The matrix allows for release, usually sustained release, of the entrapped agent. The stent and matrix is sheathed with a covalently bound gel. In one embodiment of the invention, the stent is used to deliver therapeutic agents to a patient, providing the advantage of efficient delivery and sustained release of an agent at a localized site. In another embodiment of the invention, the drug delivery system is used for testing and comparison of candidate drugs in an in vivo setting.
1. A platform for localized delivery of a biologically active agent, comprising:
a stent comprising channels on one or both of the adluminal and abluminal surfaces, wherein contained within said channels is a matrix of microspheres in which a biologically active agent is entrapped; said stent being ensheathed in a gel covalently bound to the stent surface, which gel fills unoccupied spaces within the channels and between said microspheres.
2. The platform according to claim 1 , wherein said gel is additionally covalently bound to said matrix.
3. The platform according to claim 1 , wherein said stent is formed of a biologically compatible metal.
4. The platform according to claim i, wherein said stent is a polymeric biodegradable or erodible stent.
5. The platform according to claim i, wherein said channels are from 10 to 200 μm in depth.
6. The platform according to claim 5 , wherein said channels extend end to end, or the entire circumference of the stent.
7. The platform according to claim 5 , wherein said channels are adluminal.
8. The platform according to claim 5 , wherein said channels are abluminal.
9. The platform according to claim 5 , wherein said channels are at least about 10 μm in width.
10. The platform according to claim 5 , wherein said channels are tapered.
11. The platform according to claim 1 , wherein said stent surface is modified with an adhesion agent for covalent binding.
12. The platform according to claim 11 , wherein said stent is comprised of a biologically compatible metal, and said adhesion agent is a silane coupling reagent.
13. The platform according to claim 1 , wherein said particles are microspheres of about 1 to 100 μm in diameter.
14. The platform according to claim 1 , wherein said matrix is covalently bound to said gel.
15. The platform according to claim 1 , wherein said matrix is comprised of a biodegradable polymer.
16. The platform according to claim 14 , wherein said biodegradable polymer comprises one or more of D-lactic acid, L-lactic acid, racemic lactic acid, glycolic acid and polycaprolactone.
17. The platform according to claim 1 , wherein said matrix is comprised of a biocompatible, non-biodegradable polymer.
18. The platform according to claim 1 , wherein said gel comprises methacrylate.
19. The platform according to claim 1 , wherein said biologically active agent is a pharmacologically active drug.
20. The platform according to claim 1 , wherein said biologically active agent is a protein.
21. The platform according to claim 1 , wherein said biologically active agent is a nucleic acid.
22. The platform according to claim 1 , wherein said biologically active agent inhibits in-stent restenosis.
23. The platform according to claim 22 , wherein said biologically active agent is rapamycin.
24. The platform according to claim 22 , wherein said biologically active agent is an inhibitor of GPIIb/IIIa.
25. The platform according to claim 24 , wherein said inhibitor is RheoPro.
26. A method for localized delivery of a biologically active agent, comprising:
implanting in the lumen of a vessel a stent comprising channels on one or both of the adluminal and abluminal surfaces, wherein contained within said channels is a matrix of microspheres in which a biologically active agent is entrapped; said stent being ensheathed in a gel covalently bound to the stent surface; which gel fills unoccupied spaces within the channels and between said microspheres;
wherein said biologically active agent is released from said matrix.
27. The method according to claim 26 , wherein said matrix is covalently bound to said gel.
28. The method according to claim 26 , wherein said stent is formed of a biologically compatible metal.
29. The method according to claim 26 , wherein said stent is a polymeric biodegradable or erodible stent.
30. The method according to claim 26 , wherein said channels are from 10 to 200 μm in depth.
31. The method according to claim 26 , wherein said channels extend end to end, or the entire circumference of the stent.
32. The method according to claim 30 , wherein said channels are adluminal.
33. The method according to claim 30 , wherein said channels are abluminal.
34. The method according to claim 30 , wherein said channels are at least about 10 μm in width.
35. The method according to claim 30 , wherein said stent surface is modified with an adhesion agent for covalent binding.
36. The method according to claim 35 , wherein said stent is comprised of a biologically compatible metal, and said adhesion agent is a silane coupling reagent.
37. The method according to claim 27 , wherein said particles are microspheres of about 1 to 100 μm in diameter.
38. The method according to claim 27 , wherein said matrix is comprised of a biodegradable polymer.
39. The method according to claim 38 , wherein said biodegradable polymer comprises one or more of D-lactic acid, L-lactic acid, racemic lactic acid, glycolic acid and polycaprolactone.
40. The method according to claim 27 , wherein said matrix is comprised of a biocompatible, non-biodegradable polymer.
41. The method according to claim 26 , wherein said gel comprises methacrylate.
42. The method according to claim 26 , wherein said biologically active agent is a pharmacologically active drug.
43. The method according to claim 26 , wherein said biologically active agent is a protein.
44. The method according to claim 26 , wherein said biologically active agent is a nucleic acid.
45. The method according to claim 26 , wherein said biologically active agent inhibits in-stent restenosis.
46. The method according to claim 45 , wherein said biologically active agent is rapamycin.
47. The method according to claim 45 , wherein said biologically active agent is an inhibitor of GPIIb/IIIa.
48. The method according to claim 46 , wherein said inhibitor is RheoPro.