Nitric Oxide-Releasing Silicone Oil with Tunable Payload for Antibacterial Applications

Abstract

Bacterial infections are a hurdle to the application of medical devices, and in the United States alone, more than one million infection cases are reported annually from indwelling medical devices. Infections not only affect the function of medical devices but also risk the lives and health of patients. Nitric oxide (NO) has been used as an antibacterial therapy that kills bacteria without causing resistance and provides many therapeutic effects such as anti-inflammation, antithrombosis, and angiogenesis. Silicone oils have been widely utilized in manufacturing consumer goods, healthcare products, and medical products. Specifically, liquid silicone oils are used as a medical lubricant that creates lubricated interfaces between medical devices and the exterior physiological environment to improve the performance of medical devices. Herein, we report the first primary S-nitrosothiol-based NO-releasing silicone oil (RSNO-Si) that exhibits proactive antibacterial effects. S-nitrosothiol silicone oils (RSNO-Si) were synthesized and the NO payloads ranged from 34.0 to 603.9 μM. The increased NO payload induced higher-viscosity RSNO-Si oils, as RSNO0.1-Si, RSNO0.5-Si, and RSNO1-Si had viscosities of 12.8 ± 0.1 cP, 32.0 ± 0.2 cP, and 35.1 ± 0.3 cP, respectively. RSNO-Si-SR interfaces were fabricated by infusing silicone rubber (SR) in RSNO-Si oil, and the resulting RSNO-Si-SR disks demonstrated NO release without NO donor leaching. RSNO0.1-Si-SR, RSNO0.5-Si-SR, and RSNO1-Si-SR exhibited maximum NO flux at 0.8, 6.5, and 21.5 × 10 –10 mol cm–2 min–1 in 24 h, respectively. RSNO-Si-SR disks also demonstrated 97.45, 95.40, and 96.08% of inhibition against S. aureus in a 4 h bacterial adhesion assay. Considering the easy synthesis, simple fabrication of non-leaching NO-releasing interfaces, tunable payloads, NO flux levels, and antimicrobial effects, RSNO-Si oils exhibited their potential use as platform chemicals for creating antimicrobial medical device surfaces and other antibacterial materials.

Implantable bioelectrodes: challenges, strategies, and future directions

“…99 The IL surface of silicone oil has been used to release nitric oxide, which itself has antimicrobial and antithrombotic properties. 100 Endothelial cells tend to grow and migrate on PDMS IL surfaces, which is important for the endothelialization of implanted devices that come into contact with blood. 101 Lee et al reported a lubricated immunocapsid probe surface (LIPS) to improve performance and resist FBR.…”

Multi-component liquid-infused systems: a new approach to functional coatings

“…50 Their goal was to create an easily manufactured material that would not only release NO but also prevent one of the most significant problems facing NO-doped materials: that fouling of the surface with proteins and other biological materials would mask the interface, slowing and eventually preventing NO release. 51,52 Using a multicomponent liquid-infused system to address this was successful. NO generated by both the leaching and degradation of the SNAP within the silicone solid slowly infused into the silicone liquid, releasing NO at consistent rates (0.35-0.42 × 10 −10 mol cm −2 min −2 ) over seven days and significantly reducing platelet adhesion compared to surfaces with a liquid coating alone.…”

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

“…A similar methodology was reported with other SR-based medical devices for the use of urinary catheters and insulin cannula with long-term NO release and reduced SNAP leaching and protein fouling in addition to excellent antibacterial, antifouling, and biocompatible properties. ,, This is a simple and promising approach to generate a LINORel surfaces on prefabricated medical devices and therefore holds huge potential in clinical translation. Recently, a novel method to generate NO-releasing Si oil with proactive antibacterial properties was reported that involved covalent immobilization of the NO donor to Si oil or generation of NO-releasing Si oil by nitrosation of thiolated Si oils. , Such oils can be infused on the PDMS surfaces that are often used for biomedical device applications to create antibacterial interfaces. NO release from these surfaces can be controlled by modulating the NO payload on the basis of the type of application.…”

“…Recently, a novel method to generate NO-releasing Si oil with proactive antibacterial properties was reported that involved covalent immobilization of the NO donor to Si oil or generation of NO-releasing Si oil by nitrosation of thiolated Si oils. 208,209 Such oils can be infused on the PDMS surfaces that are often used for biomedical device applications to create antibacterial interfaces. NO release from these surfaces can be controlled by modulating the NO payload on the basis of the type of application.…”