27Resveratrol offers pleiotropic health beneficial effects including its reported capability to 28 inhibit lipopolysaccharide (LPS) induced cytokine production. The aim of this work was 29 to prepare, characterize and evaluate a resveratrol nanoparticulate formulation based 30 on zein. For this purpose the oral bioavailability of the encapsulated polyphenol as well 31 as its anti-inflammatory effect in a mouse model of endotoxic shock were studied. 32Resveratrol-loaded nanoparticles displayed sizes around 300 nm with a negative zeta 33 potential (-51 mV) and a polyphenol loading close to 80 μg/mg. In vitro, the release of 34 resveratrol from the nanoparticles was found to be pH-independent and adjusted well 35 to the Peppas-Salin kinetic model, suggesting a mechanism based on the combination 36 between diffusion and erosion of the nanoparticle matrix. Pharmacokinetic studies 37 demonstrated that zein-based nanoparticles provided high and prolonged plasma 38 levels of the polyphenol for at least 48 h. The oral bioavailability of resveratrol when 39 administered in these nanoparticles increased up to 50% (20-fold higher than for the 40 control solution of the polyphenol). Furthermore, nanoparticles administered daily for 7 41 days at 15 mg/kg, were able to diminish the endotoxic symptoms induced in mouse by 42 the ip administration of LPS (i.e. hypothermia, piloerection and stillness). In addition, 43 serum TNF-α levels were slightly lower (about 15%) of those observed for the control. 44 45
Alimentary proteins can be viewed as an adequate material for the preparation of nanoparticles and microparticles. They offer several advantages such as their digestibility, price and a good capability to interact with a wide variety of compounds and nutrients. The aim of this work was to prepare and characterize casein nanoparticles for the oral delivery of folic acid. These nanoparticles were prepared by a coacervation process, stabilized with either lysine or arginine and, finally, dried by spray-drying. For some batches, the effect of a supplementary treatment of nanoparticles (before drying) with hydrodynamic high pressure on the properties of the resulting carriers was also evaluated. The resulting nanoparticles displayed a mean size close to 150 nm and a folic acid content of around 25 mg per mg nanoparticle. From the in vitro release studies, it was observed that casein nanoparticles acted as gastro-resistant devices and, thus, folic acid was only released under simulated intestinal conditions. For the pharmacokinetic study, folic acid was orally administered to laboratory animals as a single dose of 1 mg/kg. Animals treated with folic acidloaded casein nanoparticles displayed significantly higher serum levels than those observed in animals receiving an aqueous solution of the vitamin. As a consequence the oral bioavailability of folic acid when administered in casein nanoparticles was calculated to be around 52%, a 50% higher than with the traditional aqueous solution. Unfortunately, the treatment of casein nanoparticles by hydrodynamic high pressure modified neither the release profile of the vitamin nor its oral bioavailability.
Zn and Cu interactions with three selected flavonoids (catechin, quercetin and rutin) have been electrochemically monitored. It has been shown that catechin takes 1 atom of metal per molecule; quercetin takes 2 atoms, and rutin is able to take up to 3 atoms. Not all ligands bind metals equally strong, and weakly bonded metals can be distinguished. Zn shows a sluggish kinetics and, at the same time, the highest conditional formation constants. The method could be applied to a real sample. Theoretical models are proposed for the most favourable compounds.
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