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Poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) (F127) hydrogels have been used to deliver nitric oxide (NO) topically in biomedical applications. Here, the effect of F127 microenvironments on the photochemical NO release from S-nitrosoglutathione (GSNO) was investigated in F127 solutions 7.6 wt% 15 wt% and 22.5 wt% at 15 °C and 37 °C. Small-angle X-ray Scattering (SAXS) and Differential Scanning Calorimetry (DSC) measurements, along with proton Nuclear Magnetic Resonance ( 1 H NMR) spectral shifts and T 2 relaxation data at six different concentration-temperature conditions, allowed identifying F127 microphases characterized by: a sol phase of unimers; micelles in non-defined periodic order, and a gel phase of cubic packed micelles. Kinetic measurements showed that GSNO photodecompositon proceeds faster in micellized F127 where GSNO is segregated to the intermicellar microenvironment. Real time kinetic monitoring of NO release and T 2 relaxation profiles showed that NO is preferentially partitioned into the hydrophobic PPO cores of the F127 micelles, with the consequent decrease in its rate of release to the gas phase. These results show that F127 microphases affect both the kinetics of GSNO photodecomposition and the rate of NO escape and can be used to modulate the photochemical NO delivery from F127/GSNO solutions., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Nitric oxide (NO)-mediated vasodilation plays a key role in gastric mucosal defense, and NO-donor drugs may protect against diseases associated with gastric mucosal blood flow (GMBF) deficiencies. In this study, we used the ex vivo gastric chamber method and Laser Doppler Flowmetry to characterize the effects of luminal aqueous NO-donor drug S-nitroso-N-acetylcysteine (SNAC) solution administration compared to aqueous NaNO2 and NaNO3 solutions (pH 7.4) on GMBF in Sprague-Dawley rats. SNAC solutions (600 μM and 12 mM) led to a rapid threefold increase in GMBF, which was maintained during the incubation of the solutions with the gastric mucosa, while NaNO2 or NaNO3 solutions (12 mM) did not affect GMBF. SNAC solutions (600 μM and 12 mM) spontaneously released NO at 37 °C at a constant rate of 0.3 or 14 nmol·mL-1·min-1, respectively, while NaNO2 (12 mM) released NO at a rate of 0.06 nmol·mL-1·min-1 and NaNO3 (12 mM) did not release NO. These results suggest that the SNAC-induced GMBF increase is due to their higher rates of spontaneous NO release compared to equimolar NaNO2 solutions. Taken together, our data indicate that oral SNAC administration is a potential approach for gastric acid-peptic disorder prevention and treatment.

We report herein the design, preparation and characterisation of a new, water soluble, nanoplatform for the light-triggered release of nitric oxide (NO). This nanoconstruct has been achieved by exploiting a layer-by-layer approach to assembly a polyelectrolyte modified with a NO photochemical precursor, around citrate stabilized gold colloidal template. Combined spectroscopic and transmission electron microscopy analysis show that the layered hybrid nanoparticles remain stable under physiological conditions without any significant clustering along the different coating processes. The photochemical properties of the NO photocage are well preserved upon its covalent grafting in the polymeric skeleton, before and after the of the metal colloids. The direct and in real time monitoring of NO using an ultrasensitive electrode unambiguously shows the light-stimulated NO release from modified gold nanoparticles and demonstrates that the approach used permits the accurate regulation of the NO reservoir on the nanoparticles surface., (Copyright © 2013 Elsevier Inc. All rights reserved.)

A major problem associated with nitric oxide (NO) donors is the release of the desired amount of NO at a specific site. A number of platforms have been developed for the regulation of NO dosage. We present the use of citrate-stabilized gold nanoparticles as a platform to regulate NO release. Because of the affinity between gold and thiols, the characteristic -S-NO bond of S-nitrosothiols (RSNOs) breaks in the presence of gold nanoparticles, thereby releasing NO and modifying the gold nanoparticle surface with the corresponding thiol. This system allows for surface-controlled NO release, where the amount of NO released is proportional to the number of thiols bound to the gold nanoparticle surface. Moreover, by employing an amperometric technique to detect the maximum NO release, we were able to estimate the stoichiometry of the reaction, that is, the number of adsorbed RSNO molecules per gold nanoparticle. A kinetic model for NO release and its subsequent decomposition is proposed and used to fit the experimental results. The reaction was found to be zeroth- and first-order with respect to RSNO and gold nanoparticles, respectively.