Topical antiviral compositions, delivery systems, and methods of using the same

1. A delivery system comprising a composition comprising a nitric oxide (NO)-releasing active pharmaceutical ingredient,

wherein the NO-releasing active pharmaceutical ingredient is a NO-releasing compound comprising an NO donor selected from the group consisting of a diazeniumdiolate, nitrosothiol, nitrosamine, hydroxyl nitrosamine, hydroxyl amine and hydroxyurea and the NO-releasing active pharmaceutical ingredient is present in the composition in an amount of 0.01% to 30% by weight of the composition,

wherein the composition stores and/or releases nitric oxide in an amount of about 0.05% to about 10% by weight of the composition, wherein the delivery system releases nitric oxide in a cumulative amount of at least about 90 nmol of NO/mg of the delivery system at 4 hours after administration, as measured by real time in vitro release testing, and

wherein the delivery system is in the form of a ring, suppository, and/or sponge.

2. The delivery system of claim 1 , further comprising a substrate, and wherein the composition is provided in and/or on the substrate.

3. The delivery system of claim 1 , wherein the delivery system is configured to contact the composition to the skin and/or nail of a subject.

4. The delivery system of claim 1 , wherein the nitric oxide-releasing active pharmaceutical ingredient comprises a nitric oxide-releasing compound including a diazeniumdiolate functional group.

5. The delivery system of claim 4 , wherein the nitric oxide releasing compound comprises a NO-releasing co-condensed silica particle.

6. The delivery system of claim 1 , wherein the composition has a pH of about 5 to about 11.

7. The delivery system of claim 1 , wherein the delivery system administers nitric oxide in an amount sufficient to induce apoptosis in virally infected cells.

8. The delivery system of claim 1 , wherein the delivery system administers nitric oxide in an amount sufficient to reduce or eliminate viral replication with less than about 50% host cell cytotoxicity.

9. A delivery system comprising a nitric oxide-releasing active pharmaceutical ingredient,

wherein the nitric oxide-releasing active pharmaceutical ingredient is a diazeniumdiolate-functionalized macromolecule and is present in the delivery system in an amount of 0.01% to 30% by weight of the delivery system,

wherein the delivery system releases nitric oxide in a cumulative amount of at least about 90 nmol of NO/mg of the delivery system at 4 hours after administration, as measured by real time in vitro release testing, and

wherein the delivery system comprises a ring, suppository, and/or sponge that is configured to administer nitric oxide to a cell of a subject.

10. The delivery system of claim 9 , further comprising a substrate, and wherein the nitric oxide-releasing active pharmaceutical ingredient is in and/or on the substrate.

11. The delivery system of claim 9 , wherein the delivery system is configured to contact the nitric oxide-releasing active pharmaceutical ingredient to the skin and/or nail of a subject.

12. The delivery system of claim 9 , wherein the nitric oxide releasing compound comprises a NO-releasing co-condensed silica particle.

13. The delivery system of claim 9 , wherein the delivery system administers nitric oxide in an amount sufficient to induce apoptosis in virally infected cells.

14. The delivery system of claim 9 , wherein the delivery system administers nitric oxide in an amount sufficient to reduce or eliminate viral replication with less than about 50% host cell cytotoxicity.

15. A method of administering nitric oxide to a subject, the method comprising:

contacting a delivery system to the skin and/or nail of the subject, wherein the delivery system comprises a ring, suppository, and/or sponge and comprises a nitric oxide-releasing active pharmaceutical ingredient,

wherein the nitric oxide-releasing active pharmaceutical ingredient is a diazeniumdiolate-functionalized macromolecule and is present in the delivery system in an amount of 0.01% to 30% by weight of the delivery system, and

wherein the delivery system releases nitric oxide in a cumulative amount of at least about 90 nmol of NO/mg of the delivery system at 4 hours after administration, as measured by real time in vitro release testing, thereby administering nitric oxide to the subject.

16. The method of claim 15 , wherein the delivery system further comprises a substrate and the nitric oxide-releasing active pharmaceutical ingredient is in and/or on the substrate.

17. The method of claim 15 , wherein the delivery system is configured for delivery to a body cavity of a subject.

18. The method of claim 15 , wherein the nitric oxide releasing compound comprises a NO-releasing co-condensed silica particle.

19. The method of claim 15 , wherein the delivery system is configured to administer nitric oxide to the skin and/or nail of the subject.

20. The method of claim 15 , wherein the delivery system administers nitric oxide in an amount sufficient to reduce or eliminate viral replication in the virally infected cell with less than about 50% host cell cytotoxicity.

21. The delivery system of claim 1 , wherein the NO-releasing compound comprises diazeniumdiolated co-condensed silica particles comprising a co-condensed silica network comprising methylaminopropyl trimethoxysilane (MAP3) and tetraethyl orthosilicate (TEOS).

22. The delivery system of claim 1 , wherein the NO-releasing compound comprises diazeniumdiolated co-condensed silica particles comprising a co-condensed silica network comprising methylaminopropyl trimethoxysilane (MAP3) and tetramethyl orthosilicate (TMOS).

23. The delivery system of claim 1 , wherein the NO-releasing compound comprises diazeniumdiolated co-condensed silica particles comprising a co-condensed silica network comprising N-(2-aminoethyl)-3-aminopropyltrimethoxysilane (AEAP3) and tetraethyl orthosilicate (TEOS).

24. The delivery system of claim 1 , wherein the NO-releasing compound comprises diazeniumdiolated co-condensed silica particles comprising a co-condensed silica network comprising N-(2-aminoethyl)-3-aminopropyltrimethoxysilane (AEAP3) and tetramethyl orthosilicate (TMOS).