Active Release of Nitric Oxide-Releasing Dendrimers from Electrospun Polyurethane Fibers

Abstract

The fabrication of electrospun composite polyurethane fibers capable of dual-action antibacterial dendrimer release is reported. Generation 4 (G4) poly(amidoamine) dendrimers were functionalized with octyl alkyl chain or quaternary ammonium (QA) moieties followed by modification of the resulting secondary amines with N-diazeniumdiolate nitric oxide (NO) donors to produce dual-action antibacterial dendrimers. Control and NO-releasing dendrimers were doped into polyurethane solutions prior to electrospinning of the polymer to yield well-defined dendrimer-doped composite polyurethane fibers. The fiber mats were semi-porous (≥30% porosity) and exhibited high water uptake (>100% relative to fiber mass). Dendrimer-and NOrelease characteristics (rates and totals) were dependent on the dendrimer modification and polyurethane composition, with total dendrimer-and NO-release amounts ranging from 10 -80 μg/mg and 0.027 -0.072 μmol NO/mg, respectively. The antibacterial action of the fibers was evaluated against Gram-negative and Gram-positive bacterial strains. Nitric oxide-releasing fibers demonstrated broad-spectrum bactericidal action at short (2 h) and long (24 h) timescales.

Nitric Oxide Therapy for Diabetic Wound Healing

“…Worley et al subsequently developed dual‐action antibacterial polyurethane fibers containing biocidal quaternary ammonium and NO‐releasing poly(amidoamine) dendrimers. Using two biocides improved the antibacterial efficacy and reduced the risk of resistance by way of multiple mechanistic bacterial eradication pathways . The authors reported a 4‐log reduction in bacterial viability for both Gram‐negative ( E. coli and P. aeruginosa ) and Gram‐positive ( S. aureus and methicillin‐resistant S. aureus ) bacteria.…”

Nitric Oxide–Releasing Macromolecular Scaffolds for Antibacterial Applications

“…Worley et al reported the fabrication of electrospun composite polyurethane fibers containing NOreleasing PAMAM den drimers. [99] The fibers exhibited porosity and water adsorption capacities that should enable dynamic gas and fluid exchange, requirements for effective wound dressings. The release of NO releasing PAMAM dendrimers facilitated antibacterial action.…”

S-Nitroso-N-Acetyl-D-Penicillamine Modified Hyperbranched Polyamidoamine for High-Capacity Nitric Oxide Storage and Release

“…The authors were able to fully characterize 64 armed dendrimers with the ability to deliver large, precise amounts of NO and were shown to be highly antimicrobial [18]. These types of macromolecules have then been applied to biomaterials such as polyurethane nanofibers as potential wound dressing as NO has been also to promote reendothelialization as well [19]. While this type of NO-releasing molecule is excellent for targeted therapeutics, it would be costly to integrate a large quantity of these dendrimers into polymer matrices.…”