Nitric Oxide-Releasing Fumed Silica Particles: Synthesis, Characterization, and Biomedical Application
Abstract
The preparation, characterization, and preliminary biomedical application of various nitric oxide (NO)-releasing fumed silica particles (0.2-0.3 microm) are reported. The tiny NO-releasing particles are synthesized by first tethering alkylamines onto the surface of the silica using amine-containing silylation reagents. These amine groups are then converted to corresponding N-diazeniumdiolate groups via reaction with NO(g) at high pressure in the presence of methoxide bases (e.g., NaOMe). N-Diazeniumdiolate groups were found to form more readily with secondary amino nitrogens than primary amino nitrogens tethered to the silica. Different alkali metal cations of the methoxide bases, however, have little effect on the degree of N-diazeniumdiolate formation. The N-diazeniumdiolate moieties attached on the silica surface undergo a primarily proton-driven dissociation to NO under physiological conditions, with an "apparent" reaction order somewhat greater than 1 owing to local increases in pH at the surface of the particles as free amine groups are generated. The rates of N-diazeniumdiolate dissociation are further related to the parent amine structures and the pH of the soaking buffer. The N-diazeniumdiolate groups also undergo slow thermal dissociation to NO, with zero-order dissociation observed at both -15 and 23 degrees C. It is further shown that the resulting NO-releasing fumed silica particles can be embedded into polymer films to create coatings that are thromboresistant, via the release of NO at fluxes that mimic healthy endothelial cells (EC). For example a polyurethane coating containing 20 wt % of NO-releasing particles prepared with pendant hexane diamine structure (i.e., Sil-2N[6]-N(2)O(2)Na) is shown to exhibit improved surface thromboresistivity (compared to controls) when used to coat the inner walls of extracorporeal circuits (ECC) employed in a rabbit model for extracorporeal blood circulation.
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Meyerhoff and coworkers were among the first to link NO donors to particle fillers or to polymer backbones such as PVC, polyurethane, and silicone rubber.
“Meyerhoff and coworkers were among the first to link these NO donors to particle fillers (such as fumed silica particles236) or to the polymer backbone of polymers such as PVC,34,237 polyurethane (PU),34,110,233 and silicone rubber (SR).238”
From Recent advances in thromboresistant and antimicrobial polymers for biomedical applications: just say yes to nitric oxide (NO) (2016) · cites this paper as [236]
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Self-citation
- Authors
- Zhang, H., Annich, G. M., Miskulin, J., Stankiewicz, K., Osterholzer, K., Merz, S. I., Bartlett, R. H., & Meyerhoff, M. E.
- Affiliations
- University of Michigan (US)
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2003-04-01
- Volume
- 125
- Issue
- 17
- Pages
- 5015-5024
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- OpenAlex
- W2065625962
- Cited by
- 176
- References
- 44
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 6 · 2022: 4 · 2021: 10 · 2020: 9 · 2019: 11 · 2018: 12 · 2017: 9 · 2016: 11 · 2015: 10 · 2014: 7 · 2013: 11 · 2012: 12
- FWCI
- 4.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of the American Chemical Society (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Biomedical Imaging and Bioengineering (EB 00783, R01EB000783)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Materials Science › Surfaces, Coatings and Films › Polymer Surface Interaction Studies
- Keywords
- fumed silica, N-diazeniumdiolates, silylation, NO release kinetics, pH-dependent dissociation, thermal dissociation, thromboresistance, polyurethane coatings, extracorporeal circuit
- MeSH terms
- Methanol, Amines, Animals, Azo Compounds, Extracorporeal Circulation, Hydrogen-Ion Concentration, Kinetics, Nitrites, Particle Size, Polyurethanes, Rabbits, Silicon Dioxide, Solvents, Structure-Activity Relationship, Nitric Oxide Donors, Coated Materials, Biocompatible
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