Compositions and medical devices for controlled release of nitric oxide and methods of production thereof
The present disclosure describes compositions providing for controlled release of nitric oxide (NO) and methods for production of these compositions. In some embodiments, the compositions may include a biodegradable polymer and a nitric oxide-releasing material at least partially encapsulated by the biodegradable polymer. Nitric oxide-releasing materials may include, for example, diazeniumdiolates and nitric oxide contained within a zeolite, metal-organic framework or other porous material. In general, the compositions are spun into a porous fiber, which may be further annealed by heating in order to densify the fiber. Annealing may prolong the NO release profile. Medical devices containing the compositions described herein are also contemplated by the present disclosure. Medical devices include, for example, textiles, bandages and articles of clothing.
1. A composition for controlled release of nitric oxide, comprising:
an aligned electrospun, porous fiber, wherein the fiber comprises a porous biodegradable polymer that comprises pores; and a nitric oxide-releasing material that is at least partially encapsulated by the biodegradable polymer, wherein the nitric oxide-releasing material is located within the pores of the biodegradable polymer fiber; and
a second polymer, wherein the second polymer forms a layer over the fiber and wherein the second polymer does not contain nitric oxide-releasing material.
2. The composition of claim 1 , wherein the porous biodegradable polymer is poly(lactic acid).
3. The composition of claim 1 , wherein the nitric oxide-releasing material is a diazeniumdiolate.
4. The composition of claim 1 , wherein the biodegradable polymer is hydrolysable in an aqueous solution; and
wherein a monomer produced by hydrolysis of the biodegradable polymer is operable for buffering the aqueous solution.
5. The composition of claim 1 , wherein the nitric oxide-releasing material comprises nitric oxide contained within a zeolite.
6. The composition of claim 5 , wherein the zeolite is cobalt (II)-exchanged Zeolite-A.
7. The composition of claim 1 ,
wherein a plurality of the electrospun, porous fibers are assembled into a free-standing paper.
8. The composition of claim 7 , wherein the fibers have diameters between about 100 nm and about 25 μm.
9. The composition of claim 1 , wherein the nitric oxide-releasing material is nitric oxide contained within a metal-organic framework.
10. A medical device comprising the composition of claim 1 .
11. The medical device of claim 10 , wherein the nitric oxide-releasing material is a diazeniumdiolate.
12. The medical device of claim 10 , wherein the nitric oxide-releasing material is nitric oxide contained within a zeolite.
13. The medical device of claim 10 , wherein the nitric oxide-releasing material is nitric oxide contained within a metal-organic framework.
14. The medical device of claim 10 , wherein the composition coats the surface of the medical device.
15. The medical device of claim 10 , wherein the medical device is selected from the group consisting of stents, vascular grafts, pacemaker leads, heart valves, electrodes, sensors, trocars, guide wires, catheters, ocular lenses, sling materials, sutures, wound dressing and bandages, blood collection bags and storage tubes, tubing for blood transfusions and hemodialysis, diabetic socks, and bedding.
16. The medical device of claim 10 , wherein the medical device is a textile.
17. The medical device of claim 10 , wherein the medical device is a bandage.
18. A method for preparing a composition for controlled release of nitric oxide, said method comprising:
a) providing a polymer solution comprising a biodegradable polymer dissolved in a solvent;
b) dispersing a nitric oxide-releasing material in the polymer solution; and
c) electrospinning the polymer solution into an aligned electrospun, porous fiber that contains pores and a nitric oxide-releasing material that is at least partially encapsulated by the biodegradable polymer, wherein nitric oxide-releasing material is located within the pores of the biodegradable polymer fiber; and
d) coating the aligned electrospun, porous fiber with a polymer layer, said polymer layer comprising a biodegradable polymer does not contain the nitric oxide-releasing material.
19. The method of claim 18 , wherein the nitric oxide-releasing material is a diazeniumdiolate.
20. The method of claim 18 , further comprising:
annealing the aligned electrospun, porous fiber by heating prior to coating the aligned electrospun, porous fiber.
21. A method for preparing a composition for controlled release of nitric oxide, said method comprising:
a) providing a polymer solution comprising a biodegradable polymer dissolved in a solvent;
b) dispersing a porous material in the polymer solution;
wherein the porous material is selected from the group consisting of a zeolite and a metal-organic framework;
c) electrospinning the polymer solution to form an aligned electrospun, porous fiber that contains pores and said porous material that is at least partially encapsulated by the biodegradable polymer, wherein porous material is located within the pores of the biodegradable polymer fiber;
d) impregnating the porous material with nitric oxide; and
e) coating the aligned electrospun, porous fiber with a polymer layer, said polymer layer comprising a biodegradable polymer does not contain the nitric oxide-releasing material.
22. The method of claim 21 , further comprising:
annealing the aligned electrospun, porous fiber by heating after said impregnating step.