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-N-acetylpenicillamine (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 × 10−10 mol min−1 cm−2) 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.