Electrochemically Modulated Nitric Oxide Release From Flexible Silicone Rubber Patch: Antimicrobial Activity For Potential Wound Healing Applications (original) (raw)
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ACS Applied Materials & Interfaces, 2014
A controllable and inexpensive electrochemical nitric oxide (NO) release system is demonstrated to improve hemocompatibility and reduce bacterial biofilm formation on biomedical devices. Nitric oxide is produced from the electrochemical reduction of nitrite using a copper(II)-tri(2pyridylmethyl)amine (Cu(II)TPMA) complex as a mediator, and the temporal profile of NO release can be modulated readily by applying different cathodic potentials. Single lumen and dual lumen silicone rubber catheters are employed as initial model biomedical devices incorporating this novel NO release approach. The modified catheters can release a steady, physiologicallyrelevant flux of NO for more than 7 days. Both single and dual lumen catheters with continuous NO release exhibit greatly reduced thrombus formation on their surfaces after short-term 7-h intravascular placement in rabbit veins (p < 0.02, n = 6). Three day in vitro antimicrobial experiments, in which the catheters are "turned on" for only 3 h of NO release each day, exhibit more than a 100-fold decrease in the amount of surface attached live bacteria (n = 5). These results suggest that this electrochemical NO generation system could provide a robust and highly effective new approach to improving the thromboresistance and antimicrobial properties of intravascular catheters and potentially other biomedical devices.
Journal of Investigative Dermatology, 2010
Staphylococcus aureus (SA) is a leading cause of both superficial and invasive infections in community and hospital settings, frequently resulting in chronic refractory disease. It is imperative that innovative therapeutics to which the bacteria are unlikely to evolve resistance be developed to curtail associated morbidity and mortality and ultimately improve our capacity to treat these infections. In this study, a previously unreported nitric oxide (NO)-releasing nanoparticle technology is applied to the treatment of methicillin-resistant SA (MRSA) wound infections. The results show that the nanoparticles exert antimicrobial activity against MRSA in a murine wound model. Acceleration of infected wound closure in NO-treated groups was clinically shown compared with controls. The histology of wounds revealed that NO nanoparticle treatment decreased suppurative inflammation, minimal bacterial burden, and less collagen degradation, providing potential mechanisms for biological activity. Together, these data suggest that these NO-releasing nanoparticles have the potential to serve as a novel class of topically applied antimicrobials for the treatment of cutaneous infections and wounds.
Journal of materials chemistry. B, Materials for biology and medicine, 2016
Recently, considerable research efforts have focused on increasing the biocompatibility a nd bactericidal activity of biomedical polymeric devices (e.g., catheters, etc.) through incorporation of nitric oxide (NO) releasing molecules. NO is an important endogenous molecule that is well known for enhancing blood flow via its vasodilatory activity, but it also exhibits potent antithrombotic and antimicrobial properties. In this work, we demonstrate that silicone rubber tubing can be impregnated with a tertiary S-nitrosothiol (RSNO), S-nitroso-tert-dodecylmercaptan, via a simple solvent swelling method. We further characterize the NO release and RSNO leaching from the tubing over time via use of chemiluminescence and UV/Vis spectroscopy, respectively. The tubing is shown to maintain an NO flux above the physiological levels released by endothelial cells, 0.5-4.0 × 10(-10) molcm(-2)min(-1), for more than 3 weeks while stored at 37 °C and exhibit minimal leaching. Finally, the RSNO impre...
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 2018
Methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds have become a significant clinical issue worldwide. Recently, nitric oxide (NO) has emerged as a potent antibacterial agent against MRSA infections and a wound-healing enhancer. Nevertheless, clinical applications of NO have been largely restricted by its gaseous state and short half-life. In this study, our aim was to develop S-nitrosoglutathione (GSNO, an endogenous NO donor)-loaded poly(lactic-co-glycolic acid) [PLGA] microparticles (GSNO-MPs) that release NO over a prolonged period, to accelerate the healing of MRSA-infected wounds with less frequent dosing. GSNO was successfully encapsulated into PLGA microparticles by a solid-in-oil-in-water emulsion solvent evaporation method. Scanning electron microscopy and X-ray diffraction analyses confirmed the successful fabrication of GSNO-MPs. The latter released NO in a prolonged manner over 7 days and exerted a remarkable antibacterial activity against MRSA in a conc...
Journal of Pharmaceutical Investigation, 2020
Purpose Nitric oxide (NO) has emerged as a novel agent for the treatment of infected wounds owing to its potent woundhealing effects and antibacterial activity against drug-resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). In this study, we developed a NO-releasing ointment composed of S-nitrosoglutathione (GSNO) and polyethylene glycol (PEG) for the treatment of MRSA-infected cutaneous wounds. Methods The GSNO-incorporated PEG ointment (GPO) was successfully prepared by homogeneous dispersion of micronized GSNO in a PEG ointment base. High encapsulation efficiency was achieved (97.25%) via water-free fabrication processing of the GPO, resulting in minimal GSNO hydrolysis. Results When applied to a wound, the wound fluid triggered the degradation of GSNO and NO was released from the GPO for 24 h without an initial burst release. The GPO exhibited potent antibacterial effects against MRSA without cytotoxic effects against L929 cells. An in vivo wound healing experiment using a mouse MRSA-challenged full-thickness wound model revealed that the GPO could facilitate healing of infected wounds. Conclusion Thus, the GPO could be a promising NO-releasing formulation for the treatment of infected cutaneous wounds.
Acta biomaterialia, 2014
Nitric oxide (NO) has many biological roles (e.g. antimicrobial agent, promoter of angiogenesis, prevention of platelet activation) that make NO releasing materials desirable for a variety of biomedical applications. Localized NO release can be achieved from biomedical grade polymers doped with diazeniumdiolated dibutylhexanediamine (DBHD/N2O2) and poly(lactic-co-glycolic acid) (PLGA). In this study, the optimization of this chemistry to create film/patches that can be used to decrease microbial infection at wound sites is examined. Two polyurethanes with different water uptakes (Tecoflex SG-80A (6.2±0.7wt.%) and Tecophilic SP-60D-20 (22.5±1.1wt.%)) were doped with 25wt.% DBHD/N2O2 and 10wt.% of PLGA with various hydrolysis rates. Films prepared with the polymer that has the higher water uptake (SP-60D-20) were found to have higher NO release and for a longer duration than the polyurethane with the lower water uptake (SG-80A). The more hydrophilic polymer enhances the hydrolysis rat...
Nitric oxide-releasing antibacterial albumin plastic for biomedical applications
Designing innovative materials for biomedical applications is desired to prevent surface fouling and risk of associated infections arising in the surgical care patient. In the present study, albumin plastic was fabricated and nitric oxide (NO) donor, S-nitroso-N-acetylpenicillamine (SNAP), was incorporated through a solvent swelling process. The albumin-SNAP plastic was evaluated in terms of mechanical and thermal properties, and bacterial adhesion to the plastic surface. Thermal and viscoelastic analyses showed no significant difference between albumin-SNAP plastics and pure, water-plasticized albumin samples. Bacteria adhesion tests revealed that albumin-SNAP plastic can significantly reduce the surface-bound viable gram-positive Staphylococcus aureus and gram-negative Pseudomonas aeruginosa bacterial cells by 98.7 and 98.5%, respectively, when compared with the traditional polyvi-nyl chloride medical grade tubing material. The results from this study demonstrate NO-releasing albumin plastic's potential as a material for biomedical device applications. V C 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 00B:000–000, 2018.
Pharmaceutics, 2019
The eradication of bacteria from wound sites and promotion of healing are essential for treating infected wounds. Nitric oxide (NO) is desirable for these purposes due to its ability to accelerate wound healing and its broad-spectrum antibacterial effects. We developed an in situ hydrogel-forming/NO-releasing powder dressing (NO/GP), which is a powder during storage and forms a hydrogel when applied to wounds, as a novel NO-releasing formulation to treat infected wounds. An NO/GP fine powder (51.5 μm) was fabricated by blending and micronizing S-nitrosoglutathione (GSNO), alginate, pectin, and polyethylene glycol (PEG). NO/GP remained stable for more than four months when stored at 4 or 37 °C. When applied to wounds, NO/GP absorbed wound fluid and immediately converted to a hydrogel. Additionally, wound fluid triggered a NO release from NO/GP for more than 18 h. The rheological properties of hydrogel-transformed NO/GP indicated that NO/GP possesses similar adhesive properties to mar...
Biomaterials Science, 2017
A novel dual functioning antimicrobial CarboSil 20 80A polymer material that combines physical topographical surface modification and nitric oxide (NO) release is prepared and evaluated for its efficacy in reducing bacterial adhesion in vitro. The new biomaterial is created via a soft lithography two-stage replication process to induce submicron textures on its surface, followed by solvent impregnation of the NO donor, S-nitroso-N-acetylpenicillamine (SNAP), to obtain longterm (up to 38 d) of NO release. The NO release textured polymer surface is evaluated against four bacteria commonly known to cause infections in the hospital settings and results demonstrate that the combined strategy enables a synergistic effect on reducing bacterial adhesion of Staphylococcus epidermidis and Pseudomonas aeruginosa bacteria.
Pharmaceutics, 2020
S-nitrosoglutathione (GSNO) has emerged as a potent agent for the treatment of infected cutaneous wounds. However, fabrication of GSNO-containing nanoparticles has been challenging due to its high hydrophilicity and degradability. The present study aimed to fabricate nanoparticles using newly synthesized GSNO-conjugated poly(lactic-co-glycolic acid) (PLGA) (GSNO-PLGA; GPNPs). Since hydrophilic GSNO was covalently bound to hydrophobic PLGA, loss of GSNO during the nanoparticle fabrication process was minimized, resulting in sufficient loading efficiency (2.32% of GSNO, 0.07 μmol/mg of NO). Real-time NO release analysis revealed biphasic NO release by GPNPs, including initial burst release within 3 min and continuous controlled release for up to 11.27 h, due to the differential degradation rates of the –SNO groups located at the surface and inside of GPNPs. Since GPNPs could deliver NO more efficiently than GSNO in response to increased interaction with bacteria, the former showed enh...