Antimicrobial coating for inhibition of bacterial adhesion and biofilm formation
The present invention provides antimicrobial coatings for coating substrate surfaces, particularly medical devices, for preventing bacterial adhesion and biofilm formation by inhibiting microbial growth and proliferation on the coating surface. The antimicrobial coatings are composed of a hydrogel and a bioactive agent including a substantially water-insoluble antimicrobial metallic material that is solubilized within the coating. Antimicrobial coating formulations for obtaining such coatings, and coating methods are also described.
1. A method of coating a substrate with an antimicrobial coating, the method comprising:
pre-treating a surface of the substrate with a primer layer or a surface oxidant;
preparing a solution comprising nitric acid and silver sulfadiazine;
heating the solution to a temperature between about 65° C. and about 70° C.;
adding polyvinyl alcohol to the solution to form a coating solution;
heating the coating solution to a temperature between about 75° C. and about 80° C. to solubilize the silver sulfadiazine in the coating solution;
depositing a layer of the coating solution containing solubilized silver sulfadiazine on the surface of the substrate;
crosslinking the polyvinyl alcohol within the layer to form a surface immobilized, three-dimensional hydrogel network on the substrate; and
at least partially drying the layer, wherein after at least partially drying the layer, the silver sulfadiazine remains solubilized in the layer.
2. The method of claim 1 , wherein the solution is stirred at 500 rpm for at least 15 minutes while at a temperature between about 65° C. and about 70° C., and wherein the coating solution is stirred for about 3 hours at a temperature between about 75° C. and about 80° C. to solubilize the silver sulfadiazine in the coating solution.
3. The method of claim 1 wherein pre-treating the surface of the substrate material comprises coating the surface of the substrate material with the primer layer on which the antimicrobial coating is deposited.
4. The method of claim 1 wherein pre-treating the surface of the substrate material with a surface oxidant comprises subjecting the substrate material to an oxidation process that is followed by a chemical grafting reaction rendering the surface hydrophilic, and compatible with the coating.
5. The method of claim 1 wherein the surface oxidant comprises plasma.
6. The method of claim 1 wherein the coating composition further comprises a stabilizing agent.
7. The method of claim 6 wherein the stabilizing agent is an antioxidant selected from the group consisting of lactone, phenolic, phosphite, thioester, hindered amine, hindered benozoate or hindered phenolic, and combinations thereof.
8. The method of claim 6 wherein the stabilizing agent is an antioxidant selected from the group consisting of:
1,3,5-tris(4-tert-butyl-3-hydroxy-2,6-dimethylbenzyl)-1,3,5-triazine-2,4,6-(1H,3H,5H)-trione; poly-hexamethylene; 3,5-di-t-butyl-4-hydroxybenzoic acid hexadecyl ester; alpha-tocopherol; alpha-tocopherol polyetheylene glycol succinate; alpha-lipoic acid; butylated hydroxy toluene, sodium ascorbate, and combinations thereof.
9. The method of claim 6 wherein the stabilizing agent is a photostabilizer selected from the group consisting of benzoate, benzophenone, benzotriazole, cyanoacrylate, organo nickel or organo zinc.
10. The method of claim 6 wherein the stabilizing agent is selected from the group consisting of TiO 2 , WO 3 , magnesium silicate and mixtures thereof.
11. The method of claim 10 wherein the stabilizing agent comprises TiO 2 .
12. The method of claim 1 further comprising:
chemically grafting an aliphatic alcohol onto the substrate material.
13. The method of claim 1 wherein the silver sulfadiazine is solubilized in the coating solution at a concentration between 1 mg/L and 100 g/L.