Nitric oxide-releasing nasal compositions and methods of use thereof

A composition comprising:

• a nitric oxide-releasing active pharmaceutical ingredient;
• and
• a buffer, the buffer comprising a citrate (e.g., a citrate salt) and/or citric acid in an amount of at least 100 mM.

The composition of any preceding claim, wherein the nitric oxide-releasing active pharmaceutical ingredient is suspended in the buffer.

The composition of any preceding claim, wherein the nitric oxide-releasing active pharmaceutical ingredient is present in the composition in an amount of about 0.1 mg/mL to about 30 mg/mL, optionally about 1 mg/mL to about 20 mg/mL.

The composition of any preceding claim, wherein the nitric oxide-releasing active pharmaceutical ingredient has a particle size (e.g., diameter) of about 20 nm to about 30 μm, optionally a mean particle size (e.g., mean diameter) of about 2 μm to about 20 μm.

The composition of any preceding claim, wherein the composition has an initial pH of about 4.5 to about 6.

The composition of any preceding claim, wherein the composition has a pH of about 4.5 to about 8.5, optionally wherein the composition has a pH of about 5.5.

The composition of any preceding claim, wherein the composition is configured to be aerosolized and/or atomized, optionally wherein the composition is configured for intranasal administration.

The composition of any preceding claim, wherein the composition is antiviral, optionally wherein the buffer is not antiviral and/or viricidal.

The composition of any preceding claim, wherein the composition consists of the nitric oxide-releasing active pharmaceutical ingredient and the buffer.

The composition of any preceding claim, wherein the buffer and/or composition are devoid of a diluent (e.g., devoid of a diluent other than the buffer), a co-solvent (e.g., devoid of a solvent other than the buffer), a preservative, an antioxidant, a suspending agent, a penetration enhancer, a surfactant, a viscosity-increasing agent, a humectant, a stabilizer, and/or a wetting agent.

The composition of any preceding claim, wherein the composition releases nitric oxide in an amount of about 0.001% to about 10% by weight of the composition, as measured by real time in vitro release testing, and/or the nitric oxide-releasing active pharmaceutical ingredient stores and/or releases nitric oxide in an amount of about 0.001% to about 10% by weight of the nitric oxide-releasing active pharmaceutical ingredient and/or composition, as measured by real time in vitro release testing.

The composition of any preceding claim, wherein the nitric oxide-releasing active pharmaceutical ingredient comprises a diazeniumdiolate functionalized co-condensed silica network.

The composition of any preceding claim, wherein the nitric oxide-releasing active pharmaceutical ingredient comprises a co-condensed silica network comprising diazeniumdiolated methylaminopropyl trimethoxysilane (MAP3-NONOate) and tetraethyl orthosilicate (TEOS).

The composition of any preceding claim, wherein the nitric oxide-releasing active pharmaceutical ingredient comprises a co-condensed silica network comprising diazeniumdiolated methylaminopropyl trimethoxysilane (MAP3-NONOate), ethylaminoisobutylsiloxane (EAIB3), and tetraethyl orthosilicate (TEOS).

The composition of any preceding claim, wherein the composition administers nitric oxide in an amount sufficient to induce apoptosis in virally infected cells.

The composition of any preceding claim, wherein the composition administers nitric oxide in an amount sufficient to reduce or eliminate viral replication, optionally with less than about 50% host cell cytotoxicity.