Preparation, Pharmacokinetics and Hypoglycemic Effects Evaluation of Diosgenin-Rebaudioside A Self-Assembled Nanomicelles Based on the 'Combined Drug-Excipient' Strategy

• • The optimized Dio-Reb A-SNM achieved 93.59±0.63% encapsulation efficiency and 5.65±0.07% drug loading with a particle size of 25.66±1.76 nm, enabling rapid gastrointestinal mucus penetration and enhanced cellular uptake. This sub-30 nm size is critical for avoiding first-pass metabolism and improving oral absorption. • • Relative oral bioavailability of diosgenin increased 6.82-fold compared to free diosgenin, surpassing previous formulations such as albumin nanoparticles (3.77-fold), dripping pills (4.53-fold), and amorphous solid dispersions (5.69-fold). This positions Dio-Reb A-SNM as a superior delivery system for diosgenin. • • In T2DM rats, Dio-Reb A-SNM (30 mg/kg) produced a highly significant reduction in blood glucose (P<0.01) at week 4, along with significant decreases in AST, ALT, urea nitrogen, and creatinine (P<0.01), indicating improved glycemic control and reduced hepatic and renal injury. • • The nanomicelles exhibited sustained release with 90.94% cumulative release at 18 h, following a Weibull model, combining rapid onset (tmax 2.06±0.29 h) and prolonged action (t1/2 8.39±1.94 h). This release profile supports both immediate and maintained therapeutic effects.