Nitric oxide-releasing polymers incorporating diazeniumdiolated silane derivatives
View Patent ↗Biocompatible polymeric materials capable of providing in situ release of nitric oxide (NO) included diazeniumdiolated fumed silica as a filler in a multilayer polymer structure to release NO upon contact with water (blood). The blood-contacting polymer surface is preferably multi-layered so that the NO-releasing layer, containing the diazeniumdiolated fumed silica, is shielded from blood contact by one or more top (or base) coats. When in contact with blood, the NO released at the surface of the polymer prevents platelet activation and adhesion to the surface, thereby reducing platelet consumption, risk of thrombus formation and other clinical complications associated with interactions between blood and foreign materials.
1. A thromboresistant device that releases NO at a blood-contacting surface thereof, said device comprising:
a NO-releasing layer of a polymer having dispersed therein derivatized fumed silica that has a NO-releasing diazeniumdiolate group immobilized on the silica surface; and
a coating of a biocompatible polymer on the NO-releasing layer, the coating providing the blood-contacting surface.
2. The device of claim 1 wherein there is provided at least a second coating of a polymer.
3. The device of claim 1 wherein the polymer is a medical-grade, non-biodegradable, polymer.
4. The device of claim 3 wherein the polymer is a hydrophobic polymer.
5. The device of claim 3 wherein the medical grade polymer is selected from the group of silicone rubber, poly(vinyl chloride), polyurethane, and polycaprolactone and copolymers thereof.
6. The device of claim 3 wherein the polymer in the NO-releasing layer further includes a plasticizer.
7. The device of claim 6 wherein the plasticizer is selected from the group consisting of 2-nitro octyl ether, dioctyl sebacate, isopropyl palmitate, isopropyl isostearate, and diisooctyl phthalate.
8. The device of claim 1 wherein the blood-contacting surface has an NO flux rate that is greater than, or equal to, the flux rate of NO from the endothelial cells that line the walls of all blood vessels.
9. The device of claim 8 wherein the NO flux ate is on the order of 10 −10 mole.cm −2 .min −1 .
10. The dance of claim 1 wherein the NO-releasing layer comprises:
about 30-95% by weight of a polymer;
0 to about 60% by weight plasticizer; and
from about 5-40% by weight of diazeniumdiolated fumed silica.
11. The device of claim 10 wherein the diazeniumdiolated fumed silica comprises about 10-20% by weight.