Nitric oxide (NO) is a known antibacterial agent due to its oxidative and nitrosative nature. Previous studies have demonstrated the efficacy of NO-releasing dendrimers and silica nanoparticles as novel oral therapeutics. For certain applications, the utility of these macromolecular scaffolds is limited due to lack of biodegradability and cytotoxicity concerns. Herein, we describe the development of NO-releasing hyperbranched aminoglycosides (i.e., kanamycin) as a biodegradable alternative to dendrimers and silica. The synthetic approach is straightforward and results in materials capable of storing ~0.4 µmol NO mg-1 scaffold. The antibacterial action of the hyperbranched polykanamycin was evaluated against Streptococcus mutans, Actinomyces viscosus, Porphyromonas gingivalis, and Aggregatibacter actinomycetemcomitans, key pathogens associated with dental caries and periodontal diseases. Analogous to other NO-release systems, the NO donors-modified hyperbranched polykanamycin demonstrated broad-spectrum bactericidal efficacy. At antibacterial concentrations, the scaffold also proved non-toxic to human gingival fibroblasts. Work on and comparison to other NO-releasing hyperbranched aminoglycosides (e.g., gentamicin, neomycin) will also be presented.

Nitric oxide-releasing hyperbranched polykanamycin as an oral therapeutic

253rd National Meeting (2017)

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