Fabrication of nitric oxide-releasing polyurethane glucose sensor membranes

Abstract

Despite clear evidence that polymeric nitric oxide (NO) release coatings reduce the foreign body response (FBR) and may thus improve the analytical performance of in vivo continuous glucose monitoring devices when used as sensor membranes, the compatibility of the NO release chemistry with that required for enzymatic glucose sensing remains unclear. Herein, we describe the fabrication and characterization of NO-releasing polyurethane sensor membranes using NO donor-modified silica vehicles embedded within the polymer. In addition to demonstrating tunable NO release as a function of the NO donor silica scaffold and polymer compositions and concentrations, we describe the impact of the NO release vehicle and its release kinetics on glucose sensor performance.

Nitric Oxide-Releasing Silica Nanoparticle-Doped Polyurethane Electrospun Fibers

“…2–5 In particular, macromolecular NO donor scaffolds have been the focus of much research due to their ability to store large amounts of NO and facilitate biological action. Indeed, the NO release achieved using xerogels, 6–9 silica nanoparticles, 10–12 dendrimers, 13–16 biodegradable polyesters, 17–20 and medical-grade polyurethanes 21–23 has demonstrated utility to modulate wound healing, 24, 25 kill bacteria and cancer cells, 26–28 and improve the analytical performance of chemical sensors. 29–31 Silica nanoparticles modified with NO donors represent an attractive NO-release vehicle due to straightforward synthesis, ability to achieve significant NO payloads and tunable NO-release kinetics, and their inherent low toxicity.…”

“…9, 10 Previously, we employed polymers doped with NO donor-modified silica particles to prepare NO-releasing glucose sensor membranes. 23 Nitric oxide release from the sensor membranes was tuned by altering the silica particle concentration, NO donor type, water uptake properties of the polyurethane, and the use of an overlaying polymer coating of variable thickness. 23 Unfortunately, the utility of these membranes for sensor applications was limited due to an inverse relationship between NO-release duration and analyte (i.e., glucose) permeability.…”

“…23 Nitric oxide release from the sensor membranes was tuned by altering the silica particle concentration, NO donor type, water uptake properties of the polyurethane, and the use of an overlaying polymer coating of variable thickness. 23 Unfortunately, the utility of these membranes for sensor applications was limited due to an inverse relationship between NO-release duration and analyte (i.e., glucose) permeability. 23 A more porous NO-releasing coating is thus desirable to maintain adequate analyte permeability.…”

“…23 Unfortunately, the utility of these membranes for sensor applications was limited due to an inverse relationship between NO-release duration and analyte (i.e., glucose) permeability. 23 A more porous NO-releasing coating is thus desirable to maintain adequate analyte permeability.…”

Nitric oxide release for improving performance of implantable chemical sensors – A review

“…The sensors were implanted for 10 d and analytical results were obtained comparing the NO-releasing sensors with two different NO-releasing rates with the same total amounts of NO released (3.1 μmol·cm −2 ): rapid NO release (16.0 ± 4.4 h) from N-diazeniumdiolate NO donor (MAP3/NO) [74] and slower NO release (>74.6 ± 16.6 h) from S -nitrosothiols-modified silica nanoparticles (MPTMS-RSNO). It was shown that the sensors with slower NO-release rate for extended durations exhibited a significantly lower mean absolute relative deviation (MARD) on days 1 and 3 (26.0 ± 5.1 and 23.9 ± 8.6%, respectively) versus controls (34.3 ± 10.9 and 38.8 ± 10.4%, respectively), and were characterized by shorter sensor lag time (< 4.2 min) in response to intravenous glucose tolerance tests when compared to rapid NO-releasing and controls sensors (>5.8 min) at 3, 7, and 10 d. Overall, it was shown that both rapid and slower NO-release sensors exhibited improved accuracy vs. controls and it was suggested that the materials that are capable of releasing a large amount of NO with even longer duration (i.e., several weeks) would be necessary to create the ultimate NO-release strategy for long-term implantable chemical sensing technology.…”