Multi-layered coatings and methods for controlling elution of active agents

Abstract

Embodiments of the invention include multi-layered coatings for controlling the elution rates of active agents and methods. In an embodiment, the invention includes a method of applying an elution control coating to a substrate. The method can include depositing a coating solution onto the substrate to form a base layer. The method can also include selecting a desired concentration of the solvent based on a desired elution rate. The method can further include removing solvent from the base layer to reach a desired concentration of the solvent and depositing a layer of parylene on the base layer. In an embodiment, the invention can include a medical device including a substrate, a base layer, and a porous layer. The base layer can include a polymeric matrix and an active agent dispersed within the polymeric matrix. The porous layer can include parylene. Other embodiments are also included herein.

1 . A method of applying an elution control coating to a substrate comprising:
 depositing a coating solution onto the substrate to form a base layer, the coating solution comprising an active agent, a polymer, and a solvent;   selecting a desired concentration of the solvent based on a desired elution rate;   removing solvent from the base layer to reach a desired concentration of the solvent; and   depositing a layer of parylene on the base layer.   
     
     
         2 . The method of  claim 1 , wherein depositing a coating solution onto the substrate to form a base layer comprises spraying a coating solution onto the substrate. 
     
     
         3 . The method of  claim 1 , the active agent comprising a macromolecule. 
     
     
         4 . The method of  claim 1 , the active agent selected from the group consisting of peptides and proteins. 
     
     
         5 . The method of  claim 1 , the active agent selected from the group consisting of antibodies and antibody derivatives. 
     
     
         6 . The method of  claim 1 , the solvent comprising a non-polar solvent. 
     
     
         7 . The method of  claim 1 , the solvent comprising a polar solvent. 
     
     
         8 . The method of  claim 1 , wherein depositing a coating solution onto a substrate to form a base layer comprises simultaneously spraying a first coating solution onto the substrate from a first spray head and spraying a second coating solution onto the substrate from a second spray head. 
     
     
         9 . The method of  claim 8 , the first coating solution comprising the active agent and the second coating solution comprising the polymer. 
     
     
         10 . The method of  claim 1 , the polymer comprising a degradable polymer and a non-degradable polymer, the first coating solution comprising the degradable polymer and the active agent and the second coating solution comprising non-degradable polymer. 
     
     
         11 . The method of  claim 1 , wherein removing solvent from the base layer comprises inserting the base layer and the substrate into a vacuum chamber. 
     
     
         12 . The method of  claim 1 , wherein removing solvent from the base layer comprises inserting the base layer and the substrate into a vacuum chamber for a period of time greater than about 30 minutes. 
     
     
         13 . A method of depositing a multi-layer elution control coating onto a substrate comprising:
 depositing a coating solution onto the substrate to form a base layer, the coating solution comprising an active agent, a polymer, and a solvent;   storing the substrate and base layer under vacuum for a period of time greater than about 30 minutes to form a degassed base layer; and   depositing a layer of parylene on the degassed base layer.   
     
     
         14 . A medical device comprising:
 a substrate;   a base layer disposed on the substrate, the base layer comprising a polymeric matrix and an active agent, the active agent dispersed within the polymeric matrix, the active agent selected from the group consisting of peptides, proteins, antibodies, and antibody derivatives; and   a porous layer disposed directly on the base layer, the porous layer comprising parylene.   
     
     
         15 . The medical device of  claim 14 , the base layer comprising a degradable polymer and a non-degradable polymer, the degradable polymer and the non-degradable polymer forming an interpenetrating network, the active agent dispersed within the degradable polymer. 
     
     
         16 . The medical device of  claim 14 , the polymeric matrix comprising a hydrophobic polymer. 
     
     
         17 . The medical device of  claim 14 , the polymeric matrix comprising poly-n-butylmethacrylate and polyethylene-co-vinyl acetate. 
     
     
         18 . The medical device of  claim 14 , the base layer having a thickness of between about 0.5 microns and about 100 microns. 
     
     
         19 . The medical device of  claim 14 , the top layer comprising poly(2-chloro-paraxylylene). 
     
     
         20 . The medical device of  claim 14  configured to elute about 0.1 μg/day to about 3.0 μg/day of the peptide for a period of time of at least about 30 days.