Nitric Oxide-Releasing Hyaluronic Acid as an Antibacterial Agent for Wound Therapy.

Taking advantage of their respective wound-healing roles in physiology, the dual activity of hyaluronic acid (HA) and nitric oxide (NO) was combined to create a single-agent wound therapeutic. Carboxylic acid groups of HA (6 and 90 kDa) were chemically modified with a series of alkylamines via carbodiimide chemistry to provide secondary amines for subsequent -diazeniumdiolate NO donor formation. The resulting NO-releasing HA derivatives stored 0.

Mode of nitric oxide delivery affects antibacterial action.

Nitric oxide (NO) is a broad-spectrum antibacterial agent, making it an attractive alternative to traditional antibiotics for treating infections. To date, a direct comparison of the antibacterial activity of gaseous NO (gNO) versus water-soluble NO-releasing biopolymers has not been reported. In this study, the bactericidal action of NO-releasing chitosan oligosaccharides was compared to gNO treatment against cystic fibrosis-relevant Gram-positive and Gram-negative bacteria.

Nitric oxide-releasing alginates as mucolytic agents.

The excessive production of thick, viscous mucus in severe respiratory diseases leads to obstruction of the airways and provides a suitable environment for the colonization of pathogenic bacteria. The effect of nitric oxide (NO)-releasing alginates with varying NO release kinetics on the viscoelastic properties of human bronchial epithelial (HBE) mucus was evaluated as a function of the NO-release kinetics using parallel plate rheology. Low molecular weight (~5 kDa) alginates with high NO flux (~4000 ppb/mg) and sustained release (half-life ~0.

Antibiofilm Efficacy of Nitric Oxide-Releasing Alginates against Cystic Fibrosis Bacterial Pathogens.

Colonization of the lungs by biofilm-forming pathogens is a major cause of mortality in cystic fibrosis (CF). In CF patients, these pathogens are difficult to treat due to the additional protection provided by both the biofilm exopolysaccharide matrix and thick, viscous mucus. The antibiofilm efficacy of nitric oxide (NO)-releasing alginates was evaluated against , , , and methicillin-resistant biofilms in both aerobic and anaerobic environments.

Nitric Oxide-Releasing Cyclodextrins.

A series of secondary amine-modified cyclodextrin (CD) derivatives was synthesized with diverse exterior terminal groups (i.e., hydroxyl, methyl, methoxyl, and primary amine).

Nitric Oxide-Releasing Macromolecular Scaffolds for Antibacterial Applications.

Exogenous nitric oxide (NO) represents an attractive antibacterial agent because of its ability to both disperse and directly kill bacterial biofilms while avoiding resistance. Due to the challenges associated with administering gaseous NO, NO-releasing macromolecular scaffolds are developed to facilitate NO delivery. This progress report describes the rational design and application of NO-releasing macromolecular scaffolds as antibacterial therapeutics.

Nitric Oxide-Releasing Alginates.

Low and high molecular weight alginate biopolymers were chemically modified to store and release potentially therapeutic levels of nitric oxide (NO). Carbodiimide chemistry was first used to modify carboxylic acid functional groups with a series of small molecule alkyl amines. The resulting secondary amines were subsequently converted to N-diazeniumdiolate NO donors via reaction with NO gas under basic conditions.

Role of Nitric Oxide-Releasing Chitosan Oligosaccharides on Mucus Viscoelasticity.

Nitric oxide (NO)-releasing chitosan oligosaccharides were modified with ester functional groups to examine how the mucoadhesive nature of the scaffold impacts the ability of NO to degrade mucins from human bronchial epithelial cell cultures and clinical sputum samples collected from patients with cystic fibrosis (CF). Agarose gel electrophoresis experiments indicated that the mucoadhesive NO-releasing chitosan oligosaccharides degraded both the purified mucins and sputum, while control scaffolds (without NO release or mucoadhesive ligands) had no effect on mucin structure. Microscopic observations of sputum treated with the mucoadhesive NO-releasing chitosan oligosaccharide confirmed degradation of the mucin and DNA networks.

-nitrosothiol-modified hyperbranched polyesters.

Hyperbranched polyesters with a range of exterior thiol modifications were synthesized through a Michael addition thiol-ene reaction. -Nitrosothiol nitric oxide (NO) donors were subsequently introduced onto the scaffolds to yield NO-releasing polyesters with total NO storage of ~2.0 μmol mg.