Nanosized genistein solid dispersion with superior mucus-penetrating ability significantly boosts intestinal absorption: A combined SPIP and Caco-2 cell study.

) (P < 0.05), and CLSM confirmed stronger intracellular uptake. Inhibitor studies in both SPIP and Caco-2 models demonstrated that the absorption of GEN-SD was prominently inhibited by EDTA and chlorpromazine hydrochloride (P < 0.05), indicating involvement of paracellular diffusion and clathrin-mediated endocytosis, while reserpine showed no significant effect, suggesting minimal BCRP-mediated efflux. The superior absorption of GEN-SD was attributed to the synergistic effects of amorphization, nanoscale particle size, enlarged specific surface area, improved mucus penetration, enhanced paracellular diffusion and clathrin-mediated endocytosis. This study provides a mechanistic basis for developing oral delivery systems with improved bioavailability for genistein.