Tunable nitric oxide-releasing macromolecules having multiple nitric oxide donor structures
Provided here are nitric oxide-releasing compounds that include at least two different NO donor functional groups of the same class. In some embodiments, such nitric oxide-releasing compounds are macromolecules such as dendrimer and co-condensed silica. Pharmaceutical compositions, wound dressings, kits and methods of treatments are also provided herein.
1 . A nitric oxide-releasing macromolecule comprising
at least two different NO donor structures of the same class,
wherein the at least two different NO donor structures are each nitrosothiol donors.
2 . The nitric oxide-releasing macromolecule of claim 1 , wherein the at least two different NO donor structures have different nitric oxide release kinetics.
3 . The nitric oxide-releasing macromolecule of claim 1 , wherein the nitric oxide-releasing macromolecule comprises a dendrimer.
4 . The nitric oxide-releasing macromolecule of claim 3 , wherein the dendrimer comprises at least one of a polypropyleneimine dendrimer; a polyamidoamine (PAMAM) dendrimer; a polyarylether dendrimer; a polypeptide dendrimer; a polyamide dendrimer; a dendritic polyglycerol; and a triazine dendrimer.
5 . The nitric oxide-releasing macromolecule of claim 1 , wherein the nitric oxide-releasing macromolecule comprises co-condensed silica.
6 . The nitric oxide-releasing macromolecule of claim 5 , wherein the silica is present as particles having a mean particle size of less than 10 μm.
7 . A pharmaceutical composition comprising the nitric oxide-releasing macromolecule of claim 1 , at least one excipient and, optionally, at least one additional therapeutic agent.
8 . A kit comprising at least two pharmaceutical compositions of claim 7 .
9 . A wound dressing comprising a polymer matrix and the NO releasing macromolecule of claim 1 .
10 . A kit comprising at least two wound dressings of claim 9 .
11 . A method of treating a dermatological condition, comprising topically administering the NO releasing macromolecule of claim 1 in an amount effective to actively promote healing of a wound associated with the dermatological condition.
12 . The method of claim 11 , wherein the dermatological condition comprises at least one of a wound, microbial infection and inflammation.
13 . The method of claim 11 , wherein the dermatological condition comprises acne.
14 . The nitric oxide-releasing macromolecule of claim 1 , wherein the at least two different NO donor structures are S-nitrosothiols.