Development of Poly(lipoic acid) Nanoparticles with Improved Oral Bioavailability and Hepatoprotective Effects of Quercetin.

Quercetin (QUE)-loaded poly(lipoic acid) nanoparticles (QUE/pLA) were developed to improve chemical stability in the gastrointestinal (GI) tract, oral bioavailability (BA), and pharmacological properties of QUE. QUE/pLA was prepared by emulsion solvent evaporation with ultrasonication followed by freeze-drying. Its mean particle size was 185 nm, with a high encapsulation efficiency of QUE (84.8%). QUE/pLA exhibited sustained release of QUE with improved dissolution compared with crystalline QUE and significantly enhanced chemical stability under physiological pH in the GI tract. Orally dosed QUE/pLA (50 mg QUE/kg) in rats exhibited significantly prolonged systemic exposure, possibly due to the sustained release of QUE. The oral BAs of QUE in QUE/pLA and crystalline QUE groups were 29 and 0.19%, respectively, suggesting significant enhancement of oral absorbability, likely due to the improved stability and dissolution property of QUE in the GI tracts. In hepatic injury model rats, QUE/pLA (50 mg QUE/kg) led to marked reductions in the plasma biomarker levels of alanine aminotransferase and aspartate aminotransferase by 70 and 46%, respectively, compared with the vehicle group. QUE/pLA also showed improved antioxidant potential as evidenced by the enhanced activities of hepatic glutathione, superoxide dismutase, and a decrease in the level of malondialdehyde, a marker of lipid peroxidation. Based on these findings, QUE/pLA might be a promising option to improve both the nutraceutical and pharmaceutical properties of QUE.