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 ∼0.1–0.7 × 10−10 mol cm−2 min−1 and SNAP‐FS films generate NO fluxes of ∼0–7.5 × 10−10 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. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res 72A: 409–419, 2005