Preparation and pharmacodynamic evaluation of isorhamnetin-Soluplus-TPGS mixed micelles

Isorhamnetin (ISO) is a kind of flavonoid widely found in sea buckthorn, ginkgo biloba, and other plants. It has many pharmacological activities, but poor solubility in aqueous media has limited its clinical application. In order to increase the bioavailability of ISO, we employed a thin film dispersion method to prepare ISO-loaded Soluplus-TPGS mixed polymer micelle (ISO-STM) and subsequently conducted appropriate characterizations. The micelles prepared in this work were spherical nanoparticles with uniform distribution with respective particle size (PS) and dispersion coefficient (PDI) of 81.62 ± 1.23 nm and 0.115 ± 0.020. Meanwhile, the encapsulation rate (EE) was 91.37% ± 0.82%, whereas the drug loading (DL) was 5.91% ± 0.06%. Compared to free ISO, the dissolution rate of mixed micelles (MM) significantly increased in three media. After oral administration, the oral bioavailability of MM was nearly 3 times higher than free ISO’s. In addition, the results of the zebrafish experiment showed that the anti-aging of zebrafish in the administration group was significantly better than that in the model control group. In summary, ISO-STM is a promising method with the potential to improve the solubility, and bioavailability and enhance the clinical application value of ISO.