Coating systems for the controlled delivery of hydrophilic bioactive agents
View Patent ↗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.
1. A coating system comprising (a) a polymeric basecoat layer containing one or more hydrophilic bioactive polypeptides and a polymer comprising hydrophilic and hydrophobic portions; and (b) an elution-controlling topcoat layer that comprises 100% poly(ethylene-co-vinyl acetate) copolymer wherein vinyl acetate is present in an amount in the range of 12%-25% in the copolymer.
2. The coating system of claim 1 , wherein vinyl acetate is present in an amount in the range of 12%-18% in the copolymer.
3. The coating system of claim 1 , wherein vinyl acetate is present in an amount of 18% in the copolymer.
4. The coating system of claim 1 , wherein the basecoat layer comprises (a) a first hydrophobic polymer; (b) the polymer comprising hydrophilic and hydrophobic portions; (c) optionally a second polymer; and (d) the hydrophilic bioactive agent.
5. The coating system of claim 4 , wherein the hydrophilic bioactive agent is in the form of microparticles that are dispersed within the basecoat layer.
6. The coating system of claim 4 , wherein the first hydrophobic polymer is a biostable polymer selected from the group consisting of poly(alkyl(meth)acrylates) and poly(aromatic(meth)acrylates).
7. The coating system of claim 4 , wherein the first polymer is poly(n-butyl methacrylate) (pBMA).
8. The coating system of claim 4 , wherein the second polymer comprises poly(ethylene-co-vinyl acetate) copolymer.
9. The coating system of claim 4 , wherein the polymer comprising hydrophilic and hydrophobic portions is biodegradable polymer.
10. The coating system of claim 4 , wherein the polymer comprising hydrophilic and hydrophobic portions comprises polyethylene glycol block copolymers and polyether ester copolymer.
11. The coating system of claim 4 , wherein the polymer comprising hydrophilic and hydrophobic portions comprises PEG and PBT.
12. The coating system of claim 1 , wherein the basecoat layer has a thickness ranging from about 1 μm to about 200 μm.
13. The coating system of claim 1 , wherein the basecoat layer has a thickness ranging from about 1 μm to about 50 μm.
14. The coating system of claim 1 , wherein the elution-controlling topcoat layer has thickness ranging up to about 50 μm.
15. The coating system of claim 1 , wherein the elution-controlling topcoat layer has thickness ranging from about 5 μm to about 10 μm.
16. The coating system of claim 1 , wherein the hydrophilic bioactive agent has a molecular weight of about 1000 Da or greater.
17. 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.
18. The coating system of claim 1 , wherein the hydrophilic bioactive agent comprises a Fab fragment.
19. The coating system of claim 1 , wherein the hydrophilic bioactive agent is soluble when dispersed within a solution comprising the base coat layer.