Microporous titanosilicates Cu2+- and Co2+-ETS-4 for storage and slow release of therapeutic nitric oxide

Abstract

Although nitric oxide (NO) is very toxic in low concentrations it plays a key role in the regulation of several biological systems of the human body. The potential of copper and cobalt ion-exchanged microporous titanosilicate ETS-4 for therapeutic storage and release of nitric oxide was assessed. Materials were characterized by powder X-ray diffraction, nitrogen adsorption at -196 degrees C and chemical analysis. Cation-exchanged materials showed an increased surface area and minor structural changes, relative to the parent Na-ETS-4. The NO storage and release kinetics was studied in the gas and liquid phases. NO loaded materials were also studied by diffuse reflectance infrared Fourier transform spectroscopy. The NO amounts released in the liquid phase were within the physiological range (nanomolar), while the release kinetics was slow (0.023 min(-1) for 85% release). The NO loading and release from ETS-4 were affected by the presence of Cu2+ and Co2+ cations. Assays with HeLa cells indicated that the materials have low cytotoxicity, which depends on the ion-exchanged cation. The performance of ETS-4 improved when the extra-framework Na+ cations were exchanged by Cu2+ and Co2+.