title: Nitric oxide-releasing polymers containing the [N(O)NO]- group.
abstract: Ions of structure X[N(O)NO]- display broad-spectrum pharmacological activity that correlates with the rate and extent of their spontaneous, first-order decomposition to nitric oxide when dissolved. We report incorporation of this functional group into polymeric matrices that can be used for altering the time course of nitric oxide release and/or targeting it to tissues with which the polymers are in physical contact. Structural types prepared include those in which the [N(O)NO]- group is attached to heteroatoms in low molecular weight species that are noncovalently distributed throughout the polymeric matrix, in groupings pendant to the polymer backbone, and in the polymer backbone itself. They range in physical form from films that can be coated onto other surfaces to microspheres, gels, powders, and moldable resins. Chemiluminescence measurements confirm that polymers to which the [N(O)NO]- group is attached can serve as localized sources of nitric oxide, with one prototype providing sustained NO release for 5 weeks in pH 7.4 buffer at 37 degrees C. The latter composition, a cross-linked poly-(ethylenimine) that had been exposed to NO, inhibited the in vitro proliferation of rat aorta smooth muscle cells when added as a powder to the culture medium and showed potent antiplatelet activity when coated on a normally thrombogenic vascular graft situated in an arteriovenous shunt in a baboon's circulatory system. The results suggest that polymers containing the [N(O)NO]- functional group may hold considerable promise for a variety of biomedical applications in which local delivery of NO is desired.
authors.affiliation: Department of Chemistry, University of Akron, Akron, Ohio 44325, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Smith
authors.forename: D
authors.initials: D
authors.lastname: Chakravarthy
authors.forename: S
authors.initials: S
authors.lastname: Pulfer
authors.forename: M L
authors.initials: ML
authors.lastname: Simmons
authors.forename: J A
authors.initials: JA
authors.lastname: Hrabie
authors.forename: M L
authors.initials: ML
authors.lastname: Citro
authors.forename: J E
authors.initials: JE
authors.lastname: Saavedra
authors.forename: K M
authors.initials: KM
authors.lastname: Davies
authors.forename: T C
authors.initials: TC
authors.lastname: Hutsell
authors.forename: D L
authors.initials: DL
authors.lastname: Mooradian
authors.forename: S R
authors.initials: SR
authors.lastname: Hanson
authors.forename: L K
authors.initials: LK
authors.lastname: Keefer
mesh_terms: D000818:Animals; D000838:Anions; D002455:Cell Division / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008163:Luminescent Measurements; D008297:Male; D015394:Molecular Structure; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D009569:Nitric Oxide / Q000737:chemistry / Q000378:metabolism*; D009584:Nitrogen / Q000737:chemistry; D010100:Oxygen / Q000737:chemistry; D010215:Papio; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000494:pharmacology; D011108:Polymers / Q000737:chemistry* / Q000494:pharmacology*; D013927:Thrombosis / Q000517:prevention & control
chemical_list: D000838:Anions; D010975:Platelet Aggregation Inhibitors; D011108:Polymers; D009569:Nitric Oxide; D009584:Nitrogen; D010100:Oxygen