Preparation, Pharmacokinetics and Hypoglycemic Effects Evaluation of Diosgenin-Rebaudioside A Self-Assembled Nanomicelles Based on the 'Combined Drug-Excipient' Strategy
Diosgenin (Dio) suffers from poor aqueous solubility and low oral bioavailability, limiting its clinical translation. This study developed diosgenin-rebaudioside A self-assembled nanomicelles (Dio-Reb A-SNM) using a combined drug-excipient strategy. Box-Behnken design-response surface methodology optimized the formulation: rebaudioside A to diosgenin ratio 12.32:1, diosgenin concentration 1.97 mg/mL, ultrasonic time 20.20 min. The optimized Dio-Reb A-SNM exhibited an encapsulation efficiency of 93.59±0.63%, drug loading of 5.65±0.07%, particle size of 25.66±1.76 nm, and zeta potential of -24.59±1.18 mV. Transmission electron microscopy revealed spherical morphology, and X-ray powder diffraction confirmed amorphization of diosgenin. The nanomicelles significantly enhanced saturated solubility across pH media and demonstrated sustained release (90.94% cumulative release at 18 h) fitting a Weibull model. Pharmacokinetic studies in SD rats showed that Dio-Reb A-SNM achieved a tmax of 2.06±0.29 h, t1/2 of 8.39±1.94 h, and increased Cmax and relative bioavailability by 3.59-fold and 6.82-fold, respectively, compared to free diosgenin. In a type 2 diabetes mellitus rat model, Dio-Reb A-SNM (30 mg/kg) significantly reduced blood glucose (P<0.01) and serum AST, ALT, urea nitrogen, and creatinine levels (P<0.01), with attenuated hepatic and renal pathological injury. These findings demonstrate that Dio-Reb A-SNM markedly improves oral absorption and hypoglycemic efficacy of diosgenin, providing a promising formulation strategy.