Reprint of: Nitric oxide-releasing polysaccharide derivative exhibits 8-log reduction against Escherichia coli, Acinetobacter baumannii and Staphylococcus aureus.

Health-care associated infections (HAIs) and the increasing number of antibiotic-resistant bacteria strains remain significant public health threats worldwide. Although the number of HAIs has decreased by using improved sterilization protocols, the cost related to HAIs is still quantified in billions of dollars. Furthermore, the development of multi-drug resistant strains is increasing exponentially, demonstrating that current treatments are inefficient. Thus, the quest for new methods to eradicate bacterial infection is increasingly important in antimicrobial, drug delivery and biomaterials research. Herein, the bactericidal activity of a water-soluble NO-releasing polysaccharide derivative was evaluated in nutrient broth media against three bacteria strains that are commonly responsible for HAIs. Data confirmed that this NO-releasing polysaccharide derivative induced an 8-log reduction in bacterial growth after 24h for Escherichia coli, Acinetobacter baumannii and Staphylococcus aureus. Additionally, the absence of bacteria after 72 h of exposure to NO illustrates the inability of the bacteria to recover and the prevention of biofilm formation. The presented 8-log reduction in bacterial survival after 24h is among the highest reduction reported for NO delivery systems to date, and reaches the desired standard for industrially-relevant reduction. More specifically, this system represents the only water-soluble antimicrobial to reach such a significant bacterial reduction in nutrient rich media, wherein experimental conditions more closely mimic the in vivo environment than those in previous reports. Furthermore, the absence of bacterial activity after 72 h and the versatility of using a water-soluble compound suggest that this NO-releasing polysaccharide derivative is a promising route for treating HAIs.

Nitric oxide-releasing polysaccharide derivative exhibits 8-log reduction against Escherichia coli, Acinetobacter baumannii and Staphylococcus aureus.

Health-care associated infections (HAIs) and the increasing number of antibiotic-resistant bacteria strains remain significant public health threats worldwide. Although the number of HAIs has decreased by using improved sterilization protocols, the cost related to HAIs is still quantified in billions of dollars. Furthermore, the development of multi-drug resistant strains is increasing exponentially, demonstrating that current treatments are inefficient. Thus, the quest for new methods to eradicate bacterial infection is increasingly important in antimicrobial, drug delivery and biomaterials research. Herein, the bactericidal activity of a water-soluble NO-releasing polysaccharide derivative was evaluated in nutrient broth media against three bacteria strains that are commonly responsible for HAIs. Data confirmed that this NO-releasing polysaccharide derivative induced an 8-log reduction in bacterial growth after 24h for Escherichia coli, Acinetobacter baumannii and Staphylococcus aureus. Additionally, the absence of bacteria after 72h of exposure to NO illustrates the inability of the bacteria to recover and the prevention of biofilm formation. The presented 8-log reduction in bacterial survival after 24h is among the highest reduction reported for NO delivery systems to date, and reaches the desired standard for industrially-relevant reduction. More specifically, this system represents the only water-soluble antimicrobial to reach such a significant bacterial reduction in nutrient rich media, wherein experimental conditions more closely mimic the in vivo environment than those in previous reports. Furthermore, the absence of bacterial activity after 72h and the versatility of using a water-soluble compound suggest that this NO-releasing polysaccharide derivative is a promising route for treating HAIs.

Anti-thrombogenic properties of a nitric oxide-releasing dextran derivative: evaluation of platelet activation and whole blood clotting kinetics.

Controlling platelet activation and clotting initiated by cardiovascular interventions remains a major challenge in clinical practice. In this work, the anti-thrombotic properties of a polysaccharide-based nitric oxide (NO)-releasing dextran derivative are presented. Total platelet adhesion, platelet morphology and whole blood clotting kinetics were used as indicators to evaluate the anti-clotting properties of this material. With a total NO delivery of 0.203±0.003 µmol, the NO-releasing dextran derivative (Dex-SNO) mixed with blood plasma demonstrated a significantly lower amount of platelet adhesion and activation onto a surface and reduced whole blood clotting kinetics. Nearly 75% reduction in platelet adhesion and a significant retention of platelet morphology were observed with blood plasma treated with Dex-SNO, suggesting this to be a potential anti-platelet therapeutic agent for preventing thrombosis that does not have an adverse effect on circulating platelets.

Fabrication of biodegradable polymeric nanofibers with covalently attached NO donors.

Many common wound healing aids are created from biodegradable polymeric materials. Often, these materials are unable to induce complete healing in wounds because of their failure to prevent infection and promote cell growth. This study reports the development of therapeutic materials aimed at overcoming these limitations through the release of a naturally occurring antimicrobial agent from a porous, polymeric fiber scaffold. The antimicrobial character was achieved through the release of nitric oxide (NO) while the porous structure was fabricated through electrospinning polymers into nanofibers. Three variations of the polymer poly(lactic-co-glycolic-co-hydroxymethyl propionic acid) (PLGH) modified to include thiol and NO groups were investigated. Fibers of the modified polymers exhibited smooth, bead free morphologies with diameters averaging between 200 and 410 nm. These fibers were deposited in a random manner to create a highly porous fibrous scaffold. The fibers were found to release NO under physiological pH and temperature and have the capacity to release 0.026 to 0.280 mmol NO g(-1). The materials maintained their fibrous morphological structure after this exposure to aqueous conditions. The sustained morphological stability of the fiber structure coupled to their extended NO release gives these materials great potential for use in wound healing materials.