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

Shuxian Ruan,1,* Yanli Du,2,* Xianyuan Zhang,3 Xingwang Zhang,1 Hao Kang4 1Department of Pharmaceutics, College of Pharmacy, Jinan University, Guangzhou, People’s Republic of China; 2The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 3Meizhou Baoyuantang Pharmaceutical Co., Ltd, Meizhou, People’s Republic of China; 4Department of Medicinal Chemistry and Pharmaceutical Analysis, Anhui College of Traditional Chinese Medicine, Wuhu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xingwang Zhang; Hao Kang, Email [email protected]; [email protected]: 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 N-oleoyl-1-DNJ (N-1-DNJ) and formulated it into selenized nanovesicles using a thin-film hydration method combined with in situ reduction.Results: The resulting N-1-DNJ-loaded selenized nanovesicles (N-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 N-1-DNJ-Se@NVs presented prolonged absorption, higher mean retention time, and enhanced area under the blood drug concentration versus time curve (AUC), indicating superior bioavailability. Furthermore, N-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 N-1-DNJ-Se@NVs as a promising nanomedicine for diabetes management.Keywords: 1-deoxynojirimycin, nanovesicles, selenium, sustained release, hypoglycemic effect, bioavailability