Ameliorative Hypoglycemic Effect of 1-DNJ via Structural Derivatization Followed by Assembly Into Selenized Nanovesicles.

Purpose: 1-Deoxynojirimycin (1-DNJ), a phytomedicine derived from mulberry leaves and certain bacteria, can inhibit α-glycosidase activity and alleviate insulin resistance, thereby lowering blood glucose levels. However, its short half-life and limited in vivo residence compromise its therapeutic efficacy. This study aimed to optimize the structure of 1-DNJ and develop nano-formulation to ameliorate its pharmacokinetic properties and therapeutic effects.

Methods: We synthesized -oleoyl-1-DNJ (-1-DNJ) and formulated it into selenized nanovesicles using a thin-film hydration method combined with in situ reduction.

Results: The resulting -1-DNJ-loaded selenized nanovesicles (-1-DNJ-Se@NVs) exhibited improved physiological stability and sustained release compared to non-selenized versions. In vivo pharmacokinetic studies in GK rats revealed that -1-DNJ-Se@NVs presented prolonged absorption, higher mean retention time, and enhanced area under the blood drug concentration time curve (), indicating superior bioavailability. Furthermore, -1-DNJ-Se@NVs demonstrated long-lasting hypoglycemic effect and increased cellular uptake efficiency.

Conclusion: Our findings suggest that structural derivatization improves the oral delivery of 1-DNJ and prolongs its therapeutic effect via selenized nanovesicles, positioning -1-DNJ-Se@NVs as a promising nanomedicine for diabetes management.