Anti-infective functionalized surfaces and methods of making same
Devices are provided which are functionalized to include surface regions having anti-infective agents. Methods are provided for functionalizing various material surfaces to include active surface regions for binding anti-infective agents. Methods are provided by which anti-infective moieties or agents are bonded to functionalized surfaces.
1. A method of preparing a medical device having an anti-infective surface, the method comprising
covalently bonding a functionalized organophosphonate to a native oxide surface of a metal,
derivatizing the functionalized organophosponate, and
covalently bonding a quaternary ammonium anti-infective agent to the organophosphonate,
wherein the functionalized organophosphonate is an hydroxy, amino or thiol omega-functionalized organophosphonate where the organo group is a linear or branched, saturated or unsaturated, substituted or unsubstituted, aliphatic or aromatic alkylene hydrocarbon of from 2 to 40 carbon atoms, and
comprising derivatizing the hydroxy, amino or thiol with a cross-coupling reagent;
reacting the derivatized hydroxy, amino or thiol with a diamine or aminoalcohol to bond the organo group of the organophosphonate via a urethane, carbonate, urea, thiocarbonate or thiourea bond and provide a distal amino group; and
quaternizing the distal amino.
2. The method according to claim 1 comprising covalently bonding the functionalized organophosphonate directly to the native oxide surface.
3. The method according to claim 1 comprising contacting a metal alkoxide with the native oxide surface, subjecting the metal alkoxide to conditions adequate to form a metal oxide adhesion layer, the conditions selected from the group consisting of pyrolysis, microwaving, complete or partial hydrolysis, and covalently bonding a functionalized organophosphonate to the metal oxide adhesion layer.
4. The method of claim 3 comprising contacting a zirconium alkoxide with the native oxide surface.
5. The method of claim 3 comprising contacting a zirconium alkoxide with a native oxide surface of titanium.
6. The method of claim 1 wherein the organophosphonate is 11-hydroxyundecylphosphonate.
7. The method of claim 1 wherein the the anti-infective agent is a quaternary alkylammonium moiety.
8. The method of claim 1 wherein the metal is selected from the group consisting of titanium, stainless steel, cobalt chrome, nickel, molybdenum, tantalum, zirconium, magnesium, manganese, niobium, and alloys thereof.
9. The method of claim 1 wherein the metal is titanium.