Origin of Long-Term Storage Stability and Nitric Oxide Release Behavior of CarboSil Polymer Doped with S -Nitroso- N -acetyl- d -penicillamine
Open accessAbstract
The prolonged and localized delivery of nitric oxide (NO), a potent antithrombotic and antimicrobial agent, has many potential biomedical applications. In this work, the origin of the long-term storage stability and sustained NO release mechanism of S-nitroso-N-acetyl-d-penicillamine (SNAP)-doped CarboSil 20 80A polymer, a biomedical thermoplastic silicone-polycarbonate-urethane, is explored. Long-term (22 days) localized NO release is achieved by utilizing a cross-linked silicone rubber as topcoats, which can greatly reduce the amount of SNAP, NAP, and NAP disulfide leaching from the SNAP-doped CarboSil films, as measured by LC–MS. Raman spectroscopy and powder X-ray diffraction characterization of SNAP-doped CarboSil films demonstrate that a polymer–crystal composite is formed during the solvent evaporation process when SNAP exceeds its solubility in CarboSil (ca. 3.4–4.0 wt %). Further, when exceeding this solubility threshold, SNAP exists in an orthorhombic crystal form within the bulk of the polymer. The proposed mechanism of sustained NO release in SNAP-doped CarboSil is that the solubilized SNAP in the polymer matrix decomposes and releases NO, primarily in the water-rich regions near the polymer/solution interface, and the dissolved SNAP in the bulk polymeric phase becomes unsaturated, resulting in the dissolution of crystalline SNAP within the bulk of the polymer. This is a very slow process that ultimately leads to NO release at the physiological flux levels for >3 weeks. The increased stability of SNAP within CarboSil is attributed to the intermolecular hydrogen bonds between the SNAP molecules that crystallize. This crystallization also plays a key role in maintaining RSNO stability within the CarboSil polymer for >8 months at 37 °C (88.5% remains). Further, intravascular catheters fabricated with this new material are demonstrated to significantly decrease the formation of Staphylococcus aureus biofilm (a leading cause of nosocomial bloodstream infections) (in vitro) over a 7 day period, with 5 log units reduction of viable cell count on catheter surfaces. It is also shown that the NO release catheters can greatly reduce thrombus formation on the catheter surfaces during 7 h implantation in rabbit veins, when compared to the control catheters fabricated without SNAP. These results suggest that the SNAP-doped CarboSil system is a very attractive new composite material for creating long-term NO release medical devices with increased stability and biocompatibility.
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Wo, Y., Brisbois, E. J., Bartlett, R. H., & Meyerhoff, M. E. (2016) · Biomaterials Science · doi:10.1039/c6bm00271d · Cited by 251 · see citing works
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- Authors
- Wo, Y., Li, Z., Brisbois, E. J., Colletta, A., Wu, J., Major, T. C., Xi, C., Bartlett, R. H., Matzger, A. J., & Meyerhoff, M. E.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Meyerhoff, Mark E.
- ORCID
- Venue
- ACS Applied Materials & Interfaces
- Publisher
- American Chemical Society (ACS)
- Published
- 2015-09-22
- Volume
- 7
- Issue
- 40
- Pages
- 22218-22227
- ISSN
- 1944-8244 (ISSN-L)
- 1944-8252
- PMC
- PMC4613868
- OpenAlex
- W2263818063
- Cited by
- 128
- References
- 54
- Citations by year
- 2026: 13 · 2025: 6 · 2024: 16 · 2023: 8 · 2022: 17 · 2021: 14 · 2020: 8 · 2019: 17 · 2018: 8 · 2017: 12 · 2016: 7 · 2015: 1
- FWCI
- 5.18
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- ACS Applied Materials & Interfaces (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM106180)
- National Institute of Diabetes and Digestive and Kidney Diseases (R41-DK101206-01)
- National Institute of Biomedical Imaging and Bioengineering (EB-000783)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- nitric oxide delivery, sustained drug release, storage stability, hydrogen bonding, Staphylococcus aureus biofilm, catheter-related thrombosis, intravascular catheters
- MeSH terms
- Animals, Fibrinolytic Agents, Hydrogen Bonding, Nitric Oxide, Polycarboxylate Cement, Polymers, Rabbits, Silicon, Spectrum Analysis, Raman, Staphylococcus aureus, Surface Properties, Thrombosis, Urethane, X-Ray Diffraction, Biofilms, S-Nitroso-N-Acetylpenicillamine
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