Nanometerizing Taxifolin Into Selenized Liposomes to Ameliorate Its Hypoglycemic Effect by Optimizing Drug Release and Bioavailability.

PURPOSE: Diabetes mellitus (DM) remains a significant health challenge, with traditional treatments often failing to provide lasting solutions. Taxifolin (Tax), a potential phytomedicine with antioxidant and anti-hyperglycemic properties, suffers from low water solubility and poor bioavailability, necessitating advanced delivery systems. This study aims to nanometerize taxifolin (Tax) into selenized liposomes (Tax-Se@LPs) for enhanced oral delivery and hypoglycemic effect.

METHODS

Tax-Se@LPs were fabricated through a thin-film hydration/in situ reduction technique. The resulting nanomedicine was characterized through in vitro release studies, pharmacokinetic and pharmacodynamic evaluations, cellular uptake assays, and formulation stability tests.

RESULTS

The optimized Tax-Se@LPs demonstrated an average particle size of 185.3 nm and an entrapment efficiency of 95.25% after optimization. In vitro release studies revealed that Tax-Se@LPs exhibited a slower and more sustained release profile compared to conventional liposomes, favoring gastrointestinal drug absorption. Pharmacokinetic evaluations in normal rats indicated that Tax-Se@LPs achieved a relative bioavailability of 216.65%, significantly higher than Tax suspensions and unmodified liposomes. Furthermore, in diabetic GK rats, Tax-Se@LPs resulted in a maximal blood glucose reduction of 46.8% and exhibited a more sustained therapeutic duration compared to other formulations. Cellular uptake tests manifested that selenization altered the internalization mechanisms of liposomes while preserving their absorption aptness by intestinal epithelial cells. The physiological and in vitro stability of Tax-Se@LPs was also reinforced by selenization.

CONCLUSION

Overall, Tax-Se@LPs not only improve the oral bioavailability of Tax but also enhance its therapeutic efficacy. These findings underscore the potential of Tax-Se@LPs as a promising therapeutic strategy for DM management.