Zein-Based Nanoparticles Improve the Oral Bioavailability of Resveratrol and Its Anti-inflammatory Effects in a Mouse Model of Endotoxic Shock

Abstract

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

Beneficial action of resveratrol: How and why?

“…These observations suggest that sometimes lower dose of diet-derived agents are more effective than higher doses to prevent cancer. These results emphasize the need to perform a dose response studies and develop better methods to deliver diet-derived chemopreventive molecules such as resveratrol reach the target tissues by using modern technologies such as microencapsulation or nanoparticles(57,58) to derive their beneficial actions. after warm ischemia and reperfusion in rat liver.…”

Synthesis and Biological Evaluation of Novel Resveratrol-NSAID Derivatives as Anti-inflammatory Agents

“…9,10) Additionally, resveratrol has been shown to be capable of inhibiting lipopolysaccharide (LPS) induced inflammatory response. 11,12) A lot of preclinical findings have demonstrated that resveratrol is well tolerated and non-toxic. 13) It has been reported that gastric toxicity of NSAIDs are largely dependent on the presence of the carboxylic group, 14) therefore, NSAIDs esterified with resveratrol may be a new approach to retaining anti-inflammatory properties while reducing side effects.…”

Diet, food components and the intestinal barrier

“…Oral administration of resveratrol formulated in a zein‐protein nanoparticle increased the oral bioavailability compared to resveratrol solution, reduced rectal temperature and reduced serum TNFα levels in the LPS‐induced endotoxic shock mouse model (Penalva et al . ).…”