Nitric Oxide-Releasing Polymers Containing the [N(O)NO]- Group

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...

Full description

Saved in:
Bibliographic Details
Published in:Journal of medicinal chemistry 1996-03, Vol.39 (5), p.1148-1156
Main Authors: Smith, Daniel J, Chakravarthy, Debashish, Pulfer, Sharon, Simmons, Maia L, Hrabie, Joseph A, Citro, Michael L, Saavedra, Joseph E, Davies, Keith M, Hutsell, Thomas C, Mooradian, Daniel L, Hanson, Stephen R, Keefer, Larry K
Format: Article
Language:English
Subjects:
Animals
Anions
Applied sciences
Biological and medical sciences
Blood. Blood coagulation. Reticuloendothelial system
Cell Division - drug effects
Chemical Phenomena
Chemistry, Physical
Exact sciences and technology
Hydrogen-Ion Concentration
Kinetics
Luminescent Measurements
Male
Medical sciences
Molecular Structure
Muscle, Smooth, Vascular - cytology
Nitric Oxide - chemistry
Nitric Oxide - metabolism
Nitrogen - chemistry
Organic polymers
Oxygen - chemistry
Papio
Pharmacology. Drug treatments
Physicochemistry of polymers
Platelet Aggregation Inhibitors - chemistry
Platelet Aggregation Inhibitors - pharmacology
Polymers - chemistry
Polymers - pharmacology
Properties and characterization
Special properties (catalyst, reagent or carrier)
Thrombosis - prevention & control
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 °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.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm950652b