Prevention of medical device infections via multi‐action nitric oxide and chlorhexidine diacetate releasing medical grade silicone biointerfaces

Abstract

The presence of bacteria and biofilm on medical device surfaces has been linked to serious infections, increased health care costs, and failure of medical devices. Therefore, antimicrobial biointerfaces and medical devices that can thwart microbial attachment and biofilm formation are urgently needed. Both nitric oxide (NO) and chlorhexidine diacetate (CHXD) possess broad-spectrum antibacterial properties. In the past, individual polymer release systems of CHXD and NO donor S-nitroso-Nacetylpenicillamine (SNAP) incorporated polymer platforms have attracted considerable attention for biomedical/therapeutic applications. However, the combination of the two surfaces has not yet been explored. Herein, the synergy of NO and CHXD was evaluated to create an antimicrobial medical-grade silicone rubber. The 10 wt% SNAP films were fabricated using solvent casting with a topcoat of CHXD (1, 3, and 5 wt%) to generate a dual-active antibacterial interface. Chemiluminescence studies confirmed the NO release from SNAP-CHXD films at physiologically relevant levels (0.5-4 Â 10 À10 mol min À1 cm À2 ) for at least 3 weeks and CHXD release for at least 7 days. Further characterization of the films via SEM-EDS confirmed uniform distribution of SNAP and presence of CHXD within the polymer films without substantial morphological changes, as confirmed by contact angle hysteresis. Moreover, the dual-active SNAP-CHXD films were able to significantly reduce Escherichia coli and Staphylococcus aureus bacteria (>3-log reduction) compared to controls with no explicit toxicity towards mouse fibroblast cells. The synergy between the two potent antimicrobial agents will help combat bacterial contamination on biointerfaces and enhance the longevity of medical devices.

S-Nitroso-N-acetylpenicillamine grafted silicone oil for antibacterial interface applications

“…These results suggested that the SNAP–Si–SR surface became more hydrophobic than the controls and had similar hydrophobicity like SNAP impregnated silicone materials (104–110°) reported in prior literature. 31,68–70…”

“…75 Comparable results have been reported in the literature with NO-releasing materials that show decreased bactericidal efficiency against E. coli and other Gram-negative bacteria. 68,76…”

“…75 Comparable results have been reported in the literature with NO-releasing materials that show decreased bactericidal efficiency against E. coli and other Gramnegative bacteria. 68,76 Previous reports on SNAP-based biomaterials have demonstrated the antimicrobial effects against various pathogenic bacteria and fungus strains in medical device-related infections such as P. aeruginosa, S. epidermidis, and C. albicans. [77][78][79] Nevertheless, these prior studies involved either blending or impregnating the materials with NO donor SNAP, which are often challenged by leaching of the small molecule NO donors that delocalizes the NO release from the polymer surfaces.…”

Recent Developments in Multifunctional Antimicrobial Surfaces and Applications toward Advanced Nitric Oxide-Based Biomaterials

“…Surface modifications of NO-releasing antibacterial polymer coatings are attempted to bestow additional antibacterial properties to synergistically combat bacteria. These techniques involve incorporation of the NO donor along with secondary antibacterial agents such as nanoparticles, antibiotics, antimicrobial peptides, and other antiseptic molecules . The reported studies usually contain a NO donor incorporated into the base polymer, which is top-coated with a polymer containing secondary active molecules (see Table ).…”

“…Hence, approaches that involve other clinically available antimicrobial catheter materials have also been combined with NO-releasing properties to create multifunctional medical device interfaces for a greater level of microbial eradication. Recently, a method to modify silicone rubber medical device interfaces to incorporate the NO donor SNAP and the commonly used broad-spectrum antiseptic chlorhexidine (CHXD) was reported . The antiseptic CHXD was top-coated on the SNAP-loaded surface at various concentrations.…”