IP Library › Granted Patent US 12,257,314
Granted Patent B2
US 12,257,314 · App. 17/435,313 · Granted Mar 25, 2025

Extended nitric oxide-releasing polymers via functionalized mesoporous silica nanoparticles

Inventors: Mark H. Schoenfisch (Chapel Hill, NC); Maggie Malone-Povolny (Carrboro, NC)
Assignee: The University of North Carolina at Chapel Hill
A61K47/6923A61K9/146A61K33/00A61K47/6929
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Quick Facts
Patent No.
US 12,257,314
App. No.
17/435,313
Granted
Mar 25, 2025
Kind
B2
Abstract

The subject matter disclosed herein is directed to nitric oxide releasing particles comprising a mesoporous silica network. Also disclosed are compositions comprising one or more nitric-oxide releasing particles and a polymer. In one aspect, the particles are admixed with the polymer. The compositions exhibit high payloads of nitric oxide release without particle leaching or the need for extremely cold storage conditions.

Claims (25)

1. A nitric oxide releasing particle, comprising:

nitric oxide donors;

a mesoporous silica network; and

an exterior surface,

wherein said nitric oxide donors are present within pores of said mesoporous silica network and on the exterior surface of said particle,

wherein said nitric oxide releasing particle comprises an amount of nitric oxide donors such that the particle exhibits a total nitric oxide release duration of at least 49 hours, and

wherein said nitric oxide donors are nitrosothiols.

2. The nitric oxide releasing particle of claim 1 , having a surface area sufficient for said amount of nitric oxide donors such that the particle exhibits a total nitric oxide release duration of at least 49 hours.

3. The nitric oxide releasing particle of claim 1 , wherein said silica network comprises a material selected from the group consisting of N-(2-aminoethyl)-3-aminopropyltrimethoxysilane (AEAP3), N-(6-aminohexyl)aminopropyltrimethoxysilane (AHAP3), 3-aminopropyltriethoxysilane (APTES), isobutyltrimethoxysilane (BTMS), N-methylaminopropyltrimethoxysilane (MAP3), (3-mercaptopropyl)trimethoxysilane (MPTMS), tetraethylorthosilicate (TEOS), tetramethylorthosilicate (TMOS), and 3-(trimethoxysilylpropyl)diethylenetriamine (DET3).

4. The nitric oxide releasing particle of claim 1 , wherein said silica network comprises TEOS.

5. The nitric oxide releasing particle of claim 1 , wherein said particle is etched by plasma.

6. The nitric oxide releasing particle of claim 5 , wherein said plasma is oxygen plasma.

7. The nitric oxide releasing particle of claim 1 , wherein said particle comprises activated silanols.

8. The nitric oxide releasing particle of claim 1 , wherein said particle exhibits a zeta potential of about −5.4 mV.

9. A collection of particles, wherein said collection comprises two or more particles of claim 1 , wherein said particles are monodisperse having a polydispersity index of about 0.096.

10. The nitric oxide releasing particle of claim 1 , wherein said nitric oxide donors are covalently bound to the pores of said mesoporous silica network and to the exterior surface of said particle.

11. The nitric oxide releasing particle of claim 1 , wherein said nitric oxide donors are associated with the pores of said mesoporous silica network and with the exterior surface of said particle via a non-covalent interaction selected from one of Van der Waals forces, an electrostatic force, hydrogen bonding, and a combination thereof.

12. The nitric oxide releasing particle of claim 1 , wherein said nitric oxide releasing particle has a total releasable nitric oxide storage of at least 2.00 μmol of NO per milligram of the nitric oxide releasing particle.

13. The nitric oxide releasing particle of claim 1 , wherein said nitric oxide releasing particle provides a maximum NO flux of about 1040 ppb/mg.

14. The nitric oxide releasing particle of claim 1 , wherein said nitric oxide releasing particle exhibits a half-life of about 26 hours.

15. A method of treating a disease, comprising:

administering an effective amount of the nitric oxide releasing particle of claim 1 to a subject in need thereof, wherein said disease is selected from the group consisting of a cancer, a cardiovascular disease, a microbial infection; platelet aggregation and platelet adhesion caused by the exposure of blood to a medical device; pathological conditions resulting from abnormal cell proliferation; transplantation rejections, autoimmune diseases, inflammation, vascular diseases; scar tissue; wound contraction, restenosis, pain, fever, gastrointestinal disorders, respiratory disorders, sexual dysfunctions, and sexually transmitted diseases.

16. A composition comprising a collection of particles, wherein said collection comprises one or more nitric oxide releasing particles of claim 1 , and a polymer.

17. A medical device comprising the composition of claim 16 .

18. A pharmaceutical composition comprising the nitric oxide releasing particle of claim 1 and a pharmaceutically acceptable excipient.

Assignments (5)
RELEASE OF SECURITY INTEREST Recorded Apr 8, 2025
From: CITIBANK, N.A., AS ADMINISTRATIVE AGENT
To: LIGAND PHARMACEUTICALS INCORPORATED
Reel/Frame 070776/0692 →
CORRECTION BY DECLARATION ERRONEOUSLY FILED AGAINST REEL 066350/FRAME 0942 Recorded Nov 12, 2024
From: THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL
To: THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL
Reel/Frame 069386/0419 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 18, 2024
From: NOVAN, INC.
To: LNHC, INC.
Reel/Frame 066350/0942 →
SECURITY INTEREST Recorded Oct 18, 2023
From: CYDEX PHARMACEUTICALS, INC.; LIGAND PHARMACEUTICALS INCORPORATED; METABASIS THERAPEUTICS, INC.; PFENEX INC.
To: CITIBANK, N.A., AS ADMINISTRATIVE AGENT
Reel/Frame 065271/0025 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 19, 2022
From: SCHOENFISCH, MARK H.; MALONE-POVOLNY, MAGGIE
To: THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL
Reel/Frame 058687/0179 →
Continuity (2)
Provisional Application 62812735 · Mar 1, 2019
Related Publication 20220152219A1 · May 19, 2022
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