Processes for producing polymer coatings for release of therapeutic agent
View Patent ↗A method for furnishing a therapeutic-agent-containing medical device is provided. The method comprises: (a) providing a reactive layer comprising a cross-linking agent on a medical device surface; and (b) subsequently applying a polymer-containing layer, which comprises a polymer and a therapeutic agent, over the reactive layer. The cross-linking agent interacts with the polymer to form a cross-linked polymeric region that comprises the therapeutic agent. Examples of medical devices include implantable or insertable medical devices, for example, catheters, balloon, cerebral aneurysm filler coils, arterio-venous shunts and stents.
1. A method for providing a therapeutic-agent-containing medical device, said method comprising: (a) providing a reactive layer comprising a cross-linking agent on a medical device surface; and (b) applying a polymer-containing layer comprising a polymer and a therapeutic agent over said reactive layer by stereo-lithographic deposition, wherein said cross-linking agent interacts with said polymer to form a cross-linked polymeric region comprising said therapeutic agent.
2. The method of claim 1 , wherein said medical device is an implantable or insertable medical device.
3. The method of claim 1 , wherein said medical device is selected from a catheter, a balloon, a cerebral aneurysm filler coil and an arterio-venous shunt.
4. The method of claim 1 , wherein said medical device is a stent.
5. The method of claim 4 , wherein said device is a vascular stent.
6. The method of claim 1 , wherein said crosslinking agent is an ionic crosslinking agent.
7. The method of claim 6 , wherein said crosslinking agent is a cationic crosslinking agent.
8. The method of claim 7 , wherein said polymer is a mono-valent poly-glycosamino-glycan polymer.
9. The method of claim 8 , wherein said polymer is sodium alginate.
10. The method of claim 8 , wherein said crosslinking agent comprises calcium cations.
11. The method of claim 1 , wherein said crosslinking agent is a covalent crosslinking agent.
12. The method of claim 11 , wherein said covalent crosslinking agent covalently bonds two amino acids.
13. The method of claim 1 , wherein said polymer-containing layer further comprises water at the time of application.
14. The method of claim 1 , wherein said therapeutic agent comprises protein.
15. The method of claim 1 , wherein said therapeutic agent comprises whole cells.
16. The method of claim 15 , wherein said therapeutic agent further comprises extracellular matrix components.
17. The method of claim 1 , wherein said therapeutic agent comprises DNA.
18. The method of claim 17 , wherein said therapeutic agent further comprises a vector for delivering said DNA.
19. The method of claim 18 , wherein said vector is a viral vector.
20. The method of claim 1 , wherein said medical device surface is a hydrophobic surface, wherein said reactive layer is provided on said hydrophobic surface in the form of an aqueous liquid comprising water and said cross-linking agent, and wherein said polymer-containing layer is applied on said reactive layer in the form an aqueous liquid comprising a polymer, a therapeutic agent and water.
21. The method of claim 1 , wherein said medical device surface is a metallic surface, wherein said reactive layer is provided on said metallic surface in the form of an aqueous liquid comprising water and an ionic cross-linking agent, and wherein said polymer-containing layer is applied on said reactive layer in the form an aqueous liquid comprising an ionically cross-linkable polymer, a therapeutic agent and water.
22. The method of claim 1 , wherein said medical device surface is a metallic surface, wherein said reactive layer is provided on said metallic surface in the form of an aqueous liquid comprising water and a cationic cross-linking agent, and wherein said polymer-containing layer is applied on said reactive layer in the form an aqueous liquid comprising a cationically cross-linkable polymer, a therapeutic agent and water.
23. The method of claim 1 , wherein the reactive layer provided prior to the application of the polymer-containing layer does not comprise a therapeutic agent.
24. The method of claim 1 , wherein the reactive layer and the polymer-containing layer are sufficiently reactive with one another such that essentially all of the polymer within the polymer-containing layer is crosslinked by the crosslinking agent.
25. A method for providing a therapeutic-agent-containing medical device, said method comprising: (a) providing a reactive layer comprising a transglutaminase crosslinking agent on a medical device surface; and (b) applying a polymer-containing layer comprising a polymer and a therapeutic agent over said reactive layer, wherein said cross-linking agent interacts with said polymer to form a cross-linked polymeric region comprising said therapeutic agent.
26. The method of claim 25 , wherein said polymer-containing layer is applied by spray coating.