Coating systems for the controlled delivery of hydrophilic bioactive agents

• US 20090280155A1
• Filed: 04/17/2009
• Published: 11/12/2009
• Est. Priority Date: 04/18/2008
• Status: Active Grant

• Current Assignee: Surmodics Incorporated
• Original Assignee: Surmodics Incorporated
• Inventors: Wormuth, Klaus R., Wadman, Shannon A., Chappa, Ralph A., Hergenrother, Robert W.
• Granted Patent: US 8,496,954 B2
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61L 2300/232 Monosaccharides, disaccharides, polysaccharides, lipopolysaccharides
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/256 Antibodies, e.g. immunoglobulins, vaccines
• CPC Class Codes: A61L 2300/258 Genetic materials, DNA, RNA, genes, vectors, e.g. plasmids
• CPC Class Codes: A61L 2300/608 having two or more layers
• CPC Class Codes: A61L 2420/08 Coatings comprising two or more layers
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: C08L 31/04 Homopolymers or copolymers of vinyl acetate

Abstract

Described are coating systems for the controlled delivery of hydrophilic bioactive agents, for example, from implantable medical devices. The coating systems of the invention comprise (a) a polymeric basecoat layer containing one or more hydrophilic bioactive agents; and (b) an elution-controlling topcoat layer that comprises a poly(ethylene-co-vinyl acetate) copolymer. The elution rate of the hydrophilic bioactive agent can be controlled by varying the vinyl acetate concentration in the elution-controlling topcoat layer.

Claims

1. A coating system of the invention comprising (a) a polymeric basecoat layer containing one or more hydrophilic bioactive agents;

and (b) an elution-controlling topcoat layer that comprises a poly(ethylene-co-vinyl acetate) copolymer.

2. The coating system of claim 1, wherein the elution-controlling topcoat layer comprises poly(ethylene-co-vinyl acetate) copolymer (pEVA) having a vinyl acetate concentration ranging from about 10% to about 50% vinyl acetate.

3. The coating system of claim 1, wherein the elution-controlling topcoat layer comprises poly(ethylene-co-vinyl acetate) copolymer (pEVA) having a vinyl acetate concentration ranging from about 15% to about 35% vinyl acetate.

4. The coating system of claim 1, wherein the elution-controlling topcoat layer comprises predominately pEVA.

5. The coating system of claim 1, wherein the elution-controlling topcoat layer comprises greater than about 50% wt. pEVA.

6. The coating system of claim 1, wherein the elution-controlling topcoat layer comprises about 90% wt. or greater pEVA.

7. The coating system of claim 1, wherein the topcoat layer further comprises one or more polymers selected from the group consisting of pBMA , alkyl methacrylates, polystyrene, or polybutadiene.

8. The coating system of claim 1, wherein the basecoat layer comprises (a) a first hydrophobic polymer;

(b) a hydrophilic/hydrophobic polymer;

(c) optionally a second polymer; and

(d) a hydrophilic bioactive agent.

9. The coating system of claim 8, wherein the hydrophilic bioactive agent is in the form of microparticles that are dispersed within the basecoat layer.

10. The coating system of claim 8, wherein the first hydrophobic polymer is a biostable polymer selected from the group consisting of poly(alkyl(meth)acrylates) and poly(aromatic(meth)acrylates).

11. The coating system of claim 8, wherein the first polymer is poly(n-butyl methacrylate) (pBMA).

12. The coating system of claim 8, wherein the second polymer comprises poly(ethylene-co-vinyl acetate) copolymer.

13. The coating system of claim 8, wherein the hydrophilic/hydrophobic polymer is biodegradable polymer.

14. The coating system of claim 8, wherein the hydrophilic/hydrophobic polymer comprises polyethylene glycol block copolymers and polyether ester copolymer.

15. The coating system of claim 8, wherein the hydrophilic/hydrophobic polymer comprises PEG and PBT.

16. The coating system of claim 1, wherein the basecoat layer has a thickness ranging from about 1 μ

m to about 200 μ

m.

17. The coating system of claim 1, wherein the basecoat layer has a thickness ranging from about 1 μ

m to about 50 μ

m.

18. The coating system of claim 1, wherein the elution-controlling topcoat layer has thickness ranging up to about 50 μ

m.

19. The coating system of claim 1, wherein the elution-controlling topcoat layer has thickness ranging from about 5 μ

m to about 10 μ

m.

20. The coating system of claim 1, wherein the hydrophilic bioactive agent comprises a hydrophilic macromolecule selected from the group consisting of polypeptides, polynucleotides, and polysaccharides.

21. The coating system of claim 1, wherein the hydrophilic bioactive agent has a molecular weight of about 1000 Da or greater.

22. The coating system of claim 1, wherein the hydrophilic bioactive agent has a molecular weight ranging from about 10,000 Da to about 200,000 Da.

23. The coating system of claim 1, wherein the hydrophilic bioactive agent comprises a Fab fragment.

24. An implantable medical devices comprising the coating system of claim 1.

25. The implantable medical device of claim 24, wherein the device is an intraocular device.

26. A method for preparing a coating system for the controlled release of a hydrophilic bioactive agent, the method comprising the steps of:

(a) providing a basecoat coating composition comprising a basecoat polymer and at least one hydrophilic bioactive agent;

(b) disposing the coating composition on the surface of a substrate to form a basecoat layer;

(c) providing a topcoat composition comprising poly(ethylene-co-vinyl acetate) copolymer; and

(d) disposing the topcoat composition over at least a portion of the basecoat layer to form the coating system.

27. The method of claim 26, wherein the step of disposing the coating composition comprises spraying the coating composition on the surface of the substrate.

28. The method of claim 26, wherein the step of disposing the topcoat composition comprises spraying the topcoat composition on the surface of the basecoat.