Synthesis, characterization, and controlled nitric oxide release from S‐nitrosothiol‐derivatized fumed silica polymer filler particles

Abstract

A new type of nitric oxide (NO)-releasing material is described that utilizes S-nitrosothiols anchored to tiny fumed silica (FS) particles as the NO donor system. The synthetic procedures suitable for tethering three different thiol species (cysteine, N-acetylcysteine, and N-acetylpenicillamine) to the surface of FS polymer filler particles are detailed. The thiol-derivatized particles are converted to their corresponding S-nitrosothiols by reaction with t-butylnitrite. The total NO loading on the resulting particles range from 21-138 nmol/mg for the three different thiol-derivatized materials [S-nitrosocysteine-(NO-Cys)-FS, S-nitroso-N-acetylcysteine (SNAC)-FS, and S-nitroso-N-acetylpenicillamine (SNAP)-FS], with SNAP-FS yielding the highest NO loading. NO can be generated from these particles when suspended in solution via the addition of copper(II) ions, ascorbate, or irradiation with visible light. The SNAC-FS and SNAP-FS particles can be blended in polyurethane and silicone rubber matrixes to create films that release NO at controlled rates. Polyurethane films containing SNAC-FS submerged in phosphate-buffered saline (pH 7.4) generate NO surface fluxes approximately 0.1-0.7x10(-10) mol cm-2 min-1 and SNAP-FS films generate NO fluxes of approximately 0-7.5x10(-10) mol cm-2 min-1 upon addition of increasing amounts of copper ions. Silicone rubber films containing SNAC-FS or SNAP-FS do not liberate NO upon exposure to copper ions or ascorbate in phosphate-buffered saline solution. However, such films are shown to release NO at rates proportional to increasing intensities of visible light impinging on the films. Such photoinitiated NO release from these composite materials offers the first NO-releasing hydrophobic polymers with an external on/off trigger to control NO generation.

S-Nitroso-N-acetyl-D-penicillamine covalently linked to polydimethylsiloxane (SNAP–PDMS) for use as a controlled photoinitiated nitric oxide release polymer

“…Although this work suggests the possibility of photoinitiated temporal and spatial control of NO release, it is limited in application by the small amount of NO available within the monolayer. Frost and Meyerhoff [13] demonstrated that RSNOs (S-nitrosocysteine, S-nitroso-N-acetyl-L-cysteine, and S-nitroso-N-acetylpenicillamine (SNAP)) can be immobilized onto the surface of fumed silica particles that can then be blended in biomedical grade silicone rubber and cast into films. These polymer films were able to generate NO when triggered by white light.…”

Wireless platform for controlled nitric oxide releasing optical fibers for mediating biological response to implanted devices

“…This limits our ability to understand how much and in what durations NO is needed and limits the total duration of NO generation capability of exogenous NO donors (i.e., NO may be released when it is not needed, depleting the finite reservoir of NO available in the polymer coating, and therefore limiting the duration of efficacy of the implanted device by reducing the life time of NO release). Work by Frost and Meyerhoff [17,18] demonstrated fumed silica deriviatized with three different RSNOs (S-nitroso-N-acetylpenicillamine, S-nitrosocysteine, and S-nitroso-acetylcysteine demonstrated modulating of NO release via photoinitiated release and a report by Halpenny et al [19] delivered NO from nitrosyl-containing material entrapped in a sol-gel cured on a polished optical fiber also demonstrate the variable release of NO with light. A method to variably control NO release and use an on/off trigger for NO generation could provide a means to release NO at the materials-tissue interface only when needed and potentially extending the functional life of an implanted probe.…”

Modulated nitric oxide delivery in three-dimensional biomaterials for vascular functionality

“…[81] In addition, for derivatized NO-releasing particles, the risk of by-product leaching from NO donor decomposition can be eliminated as they are covalently modified and physically entrapped in the polymer matrix. [82] However, more attention on toxicity is suggested when introducing particles for NO delivery, especially when nanoscale materials are applied. The smaller size of such materials increases their contacting area with biologic membrane, which may lead to an alteration of toxicity.…”