Improved oral bioavailability of dihydromyricetin using β-cyclodextrin-grafted chitosan/tocopheryl polyethylene glycol succinate nano-delivery system: preparation, characterization, in-vitro evaluation and pharmacokinetics

A stable and uniform DMY-CD-CS/TPGS nano-delivery system was prepared. • The system markedly enhances DMY uptake in Caco-2 cells and the small intestine. • NPs open tight junctions and improve paracellular permeability. • Pharmacokinetics show a significant increase in the oral bioavailability of DMY. • Offers a new oral delivery strategy for poorly-absorbed and unstable drugs. The low oral bioavailability of Dihydromyricetin(DMY), resulting from its instability and poor absorption in the gastrointestinal tract, limits its pharmaceutical applications. In order to enhance the oral bioavailability of DMY, a DMY@CD-CS/TPGS nano-delivery system was successfully prepared using β-cyclodextrin grafted with chitosan (CD-CS) and Tocopheryl Polyethylene Glycol Succinate(TPGS). The DMY@CD-CS/TPGS-NPs have a uniform particle size distribution and good stability. In vitro release studies demonstrated that the NPs exhibited a sustained-release profile under acidic conditions. In vivo and in vitro tests showed that the NPs could promote drug uptake and internalization in Caco-2 cells through multiple endocytic pathways, and disrupt epithelial tight junctions, thereby increasing paracellular absorption. Additionally, it exhibits excellent mucosal adhesion, thereby prolonging drug retention time. The intestinal segment distribution and unidirectional perfusion experiment further demonstrated that the NPs enhanced drug uptake in the duodenum, jejunum, and ileum, and increased both the absorption rate constants and the apparent permeability coefficients. Pharmacokinetic studies demonstrated that DMY@CD-CS/TPGS-NPs significantly enhanced the oral absorption of DMY, increasing the Cmax, AUC 0-t , and t 1/2 by 7.12-fold, 1.25-fold, and 14.26-fold, respectively. The relative oral bioavailability was 250.39%, representing a 2.50-fold improvement over DMY. Overall, the CD-CS/TPGS nano-delivery system represents a promising strategy for improving the oral delivery of poorly absorbable compounds such as DMY. Download: Download high-res image (149KB) Download: Download full-size image