Original ArticleZein nanoparticles for oral delivery of quercetin: Pharmacokinetic studies and preventive anti-inflammatory effects in a mouse model of endotoxemia

Zein nanoparticles were evaluated as nanocarriers to promote the oral bioavailability of quercetin and, thus, improve its anti-inflammatory effect on a mouse model of induced endotoxemia. For this purpose, the flavonoid and 2-hydroxypropyl-β-cyclodextrin were encapsulated in zein nanoparticles. The resulting nanoparticles displayed a mean size of about 300 nm and the payload was calculated to be close to 70 μg/mg nanoparticle. The release of quercetin from zein nanoparticles followed a zero-order kinetic. After oral administration, nanoparticles provided high and sustained levels of quercetin in plasma and the relative oral bioavailability was calculated to be approx. 60%. Animals treated with quercetin-loaded nanoparticles (1 dose every two days; 1 week) presented endotoxic symptoms less severe than those observed in animals treated with the oral solution of the flavonoid (1 dose every day; 1 week). This was further corroborated by the significantly low circulating TNF-alpha in the quercetin-loaded nanoparticles treated mice.

Graphical AbstractIn this work we evaluate the capability of zein-based nanoparticles, containing 2-hydroxypropyl-β-cyclodextrin as inhibitor of the presystemic metabolism, to promote the oral bioavailability and, then, the anti-inflammatory effect of quercetin. The resulting nanoparticles improved the oral bioavailability of quercetin up to 60% (4% for the control solution, Q-sol). The effect of quercetin was evaluated in an endotoxic shock model induced with bacterial lipopolysaccharide. Animals treated with quercetin-loaded nanoparticles (Q-HPCD-NPZ) presented TNF-α levels significantly lower than that observed for the control (P < 0.01) or quantified in animals treated with the oral solution of the flavonoid (P < 0.05).100