Fabrication of resveratrol-loaded soy protein isolate-glycyrrhizin nanocomplex for improving bioavailability via pH-responsive hydrogel properties

Resveratrol (RES) is a functional polyphenol that suffers from low water solubility and poor bioavailability. A novel RES-loaded soy protein isolate-dipotassium glycyrrhizinate (SPI-DG) nanocomplex (RES@SPI-DG) was designed and evaluated in this study. RES@SPI-DG was prepared using a simple but novel self-assembly ultrasonic-assisted pH-driven method. The interactions between RES and SPI-DG were non-covalent bonds, including hydrophobic interactions, hydrogen bonds, and van der Waals interactions. RES@SPI-DG exhibited high encapsulation efficiency (97.60 +/- 0.38 %) and loading capacity (8.74 +/- 0.03 %) of RES with a uniform small size (68.39 +/- 1.10 nm). RES in RES@SPI-DG was in an amorphous state and demonstrated a 24-h apparent solubility 482.53-fold higher than bare RES. RES@SPI-DG also showed strong in vitro antioxidant properties. The pHresponsive hydrogel character of SPI-DG makes it an effective intestine-targeted delivery system that could retard the release of RES in a simulated stomach and accelerate it in a simulated intestine. In animal experiments, the bioavailability of RES@SPI-DG was 5.17 times higher than that of bare RES, and the biodistribution was also significantly improved. RES@SPI-DG demonstrated a strong hepatoprotective effect against overdose acetaminophen-induced liver injury. The SPI-DG complex might be a promising nano-platform for enhancing the bioavailability and efficacy of hydrophobic polyphenols such as RES.