Nitric oxide synthase nanoparticles for treatment of vascular disease
A sustained-release composition for stimulating endothelial cell growth including a nitric oxide synthase within a nanoparticle comprising a biocompatible polymer is described. The sustained-release composition can be administered as part of a pharmaceutical composition, or can be coated on a medical device. The nitric oxide synthase-containing nanoparticles can be used in a method of inducing endothelium formation in a blood vessel.
1. A sustained-release composition for stimulating endothelial cell growth, comprising a nitric oxide synthase dispersed within the matrix of a biocompatible polymeric nanoparticle.
2. The sustained-release composition of claim 1 , wherein the nitric oxide synthase is endothelial nitric oxide synthase.
3. The sustained-release composition of claim 1 , further comprising albumin within the nanoparticle matrix.
4. The sustained-release composition of claim 1 , wherein the biocompatible polymer is a biodegradable polymer.
5. The sustained-release composition of claim 1 , wherein the biocompatible polymer is poly-( DL -lactide-co-glycolide).
6. The sustained-release composition of claim 1 , wherein the composition further comprises one or more nitric oxide synthase cofactors.
7. The sustained-release composition of claim 1 , wherein the nanoparticle is a surface modified nanoparticle.
8. The sustained-release composition of claim 1 , wherein the nanoparticle has a diameter from 10 to 300 nanometers.
9. A method of inducing endothelium formation in a blood vessel, comprising contacting the blood vessel with a nanoparticle comprising nitric oxide synthase dispersed within the matrix of a biocompatible polymeric nanoparticle.
10. The method of claim 9 , wherein the nitric oxide synthase is endothelial nitric oxide synthase.
11. The method of claim 9 , further comprising albumin within the nanoparticle.
12. The method of claim 9 , wherein the biocompatible polymer is a biodegradable polymer.
13. The method of claim 9 , wherein the biocompatible polymer is poly-( DL -lactide-co-glycolide).
14. The method of claim 9 , wherein the nanoparticle is a modified nanoparticle.
15. The method of claim 9 , wherein the endothelium formation is induced in a subject to treat or prevent negative remodeling, thrombosis, vascular fibrosis, inflammation, platelet aggregation, hyperplasia, or restenosis of the blood vessel of the subject.
16. The method of claim 15 , wherein the subject has been diagnosed as having diabetic nephrophathy.
17. The method of claim 15 , wherein the subject has been diagnosed as having a renal or hepatic disease involving endothelial dysfunction.
18. An implantable or deliverable medical device coated with a sustained-release composition for stimulating endothelial cell growth, comprising a nitric oxide synthase dispersed within the matrix of a biocompatible polymeric nanoparticle.
19. The implantable or deliverable medical device of claim 18 , wherein the nitric oxide synthase is endothelial nitric oxide synthase.
20. The implantable or deliverable medical device of claim 18 , further comprising albumin within the nanoparticle.
21. The implantable or deliverable medical device of claim 18 , wherein the biocompatible polymer is a biodegradable polymer.
22. The implantable or deliverable medical device of claim 18 , wherein the biocompatible polymer is poly-( DL -lactide-co-glycolide).
23. The implantable or deliverable medical device of claim 18 , wherein the implantable medical device is configured to fit within a blood vessel.
24. The implantable or deliverable medical device of claim 23 , wherein the implantable medical device is selected from the group consisting of vascular grafts, stents, and balloon catheters.