Enhanced Antibacterial Efficacy Against Antibiotic-resistant Bacteria Via Nitric Oxide-releasing Ampicillin Polymer Substrates

The emergence of antibiotic-resistant bacteria poses a pressing threat to global health and is a leading cause of healthcare-related morbidity and mortality. Herein, we report the fabrication of medical-grade polymers incorporated with a dual-action S-nitroso-N-acetylpenicillamine-functionalized ampicillin (SNAPicillin) conjugated molecule through a solvent evaporation process. The resulting SNAPicillin-incorporated polymer materials act as broad-spectrum antibacterial surfaces that improve the administration efficacy of conventional antibiotics through the targeted release of both nitric oxide and ampicillin. The polymer surfaces were characterized by scanning electron microscopy and static contact angle measurements. The nitric oxide (NO) release profile and diffusion of SNAPicillin from polymers were quantified using a chemiluminescence-based nitric oxide analyzer (NOA) and ultraviolet-visible (UV-vis) spectroscopy. As a result, the films had up to 2.96 × 10 mol cm of total NO released within 24 hr. In addition, >79 % of the SNAPicillin reservoir was preserved in the polymers after 24 hr of incubation in the physiological environment, indicating their longer-term NO release ability and therapeutic window for antibacterial effects. The SNAPicillin-incorporated polymers reduced the viability of adhered bacteria in culture, with >95 % reduction found against clinically relevant strains of Staphylococcus aureus (S. aureus). Furthermore, SNAPicillin-modified surfaces did not elicit a cytotoxic effect toward 3T3 mouse fibroblast cells, supporting the material's biocompatibility in vitro. These results indicate that the complementary effects of NO-release and ampicillin in SNAPicillin-eluting polymers can enhance the properties of commonly infected medical device surfaces for antibacterial purposes.