Zein based-nanoparticles improve the oral bioavailability of resveratrol and its anti-inflammatory effects in a mouse model of endotoxic shock

摘要

Resveratrol offers pleiotropic health beneficial effects including its reported capability to inhibit lipopolysaccharide (LPS) induced cytokine production. The aim of this work was to prepare, characterize and evaluate a resveratrol nanoparticulate formulation based on zein. For this purpose the oral bioavailability of the encapsulated polyphenol as well as its anti-inflammatory effect in a mouse model of endotoxic shock were studied. Resveratrol-loaded nanoparticles displayed sizes around 300 nm with a negative zeta potential (- 51 mV) and a polyphenol loading close to 80 μg/mg. In vitro, the release of resveratrol from the nanoparticles was found to be pH-independent and adjusted well to the Peppas-Salin kinetic model, suggesting a mechanism based on the combination between diffusion and erosion of the nanoparticle matrix. Pharmacokinetic studies demonstrated that zein-based nanoparticles provided high and prolonged plasma levels of the polyphenol for at least 48 h. The oral bioavailability of resveratrol when administered in these nanoparticles increased up to 50% (20-fold higher than for the control solution of the polyphenol). Furthermore, nanoparticles administered daily for 7 days at 15 mg/kg, were able to diminish the endotoxic symptoms induced in mouse by the ip administration of LPS (i.e. hypothermia, piloerection and stillness). In addition, serum TNF-α levels were slightly lower (about 15%) of those observed for the control.