TPGS Emulsified Zein Nanoparticles Enhanced Oral Bioavailability of Daidzin: <i>In Vitro</i> Characteristics and <i>In Vivo</i> Performance

A novel drug delivery system, TPGS 1000 (TPGS) emulsified zein nanoparticles (TZN), were designed with an objective to improve the oral bioavailability of daidzin, an isoflavone glycoside with estrogenic activities. Zein nanoparticles (ZN) and TZN were fabricated using an antisolvent method. They were found to be spherical in shape with a mean size around 200 nm and a low polydispersity. Their zeta potentials were about +25 mV at pH 5.5 and −23 mV at pH 7.4. Adding TPGS as an emulsifier increased the encapsulation efficiency of daidzin in ZN from 53% to 63%. Daidzin loaded TZN had a slower daidzin release compared with daidzin loaded ZN in both simulated digestive fluids and a pH 7.4 buffer. Confocal laser scanning microscopy suggested that the cellular uptake of coumarin-6 labeled TZN in human intestinal epithelial Caco-2 cells were significantly higher than fluorescent ZN. Cellular uptake and transport studies revealed that daidzin in TZN were taken up more efficiently into Caco-2 cells and transported more quickly through Caco-2 monolayer than daidzin solution. A pharmacokinetic study demonstrated that the <i>C</i>_max of daidzein in mice after oral administration of daidzin loaded TZN was 5.66 ± 0.16 μM, which was improved by 2.64-fold compared with that of daidzin solution (2.14 ± 0.04 μM). Moreover, the areas under the curve (AUC_{0–12 h}) for daidzin loaded in TZN were enhanced by 2.4-fold compared with that of daidzin solution. These results suggested that TZN could be an effective strategy to improve the oral bioavailability of isoflavone glycosides like daidzin