Self-assembled phospholipid-based mixed micelles for improving the solubility, bioavailability and anticancer activity of lenvatinib

The clinical efficacy of lenvatinib (LFT) is limited by its poor aqueous solubility and low bioavailability. In this work, LFT-loaded soy phospholipid and sodium glycocholate mixed micelles (LFT-MMs) were prepared through classical co-precipitation. And it was served as an oral administration to address these shortcomings. The preparation conditions were optimized by single-factor experiments. The mass ratio of PC, SGC and LFT, and the species of dispersing media were proved to be decisive factors in controlling the properties of LFT-MMs. The optimal LFT-MMs presented prominent enhancement (500-fold) in LFT solubility, high encapsulation efficiency (87.6 %) as well as suitable stability ( 1 month at 4 ?C). The biocompatibility of LFT-MMs was estimated by in vitro serum stability measurement and hemolysis test. It showed that serum proteins hardly adhered to the surface of LFT-MMs, and insignificant hemolytic rate (<0.5 %) was observed at the micelles concentration below 1 mg/mL. Cytotoxicity test (MTT assay) was carried out to judge the in vitro antitumor activity. LFT-MMs showed an enhanced inhibitory activity against two main kinds of differentiated thyroid cancer cells over LFT and LFT Mesylate. To estimate the in vivo oral bioavailability of LFT-MMs, SD rats were used as animal model. Notably, the relative bioavailability of LFT-MMs compared with the original form of LFT was 176.7 %. These superior characteristics indicated that the mixed micelles are promising water-soluble formulations suitable for LFT oral delivery.

Automated summary

In this study, LFT-loaded soy phospholipid and sodium glycocholate mixed micelles (LFT-MMs) were prepared to enhance the solubility and oral bioavailability of lenvatinib. The optimized LFT-MMs showed significant improvements in solubility, encapsulation efficiency, stability, and biocompatibility. In vitro and in vivo experiments demonstrated enhanced antitumor activity and relative bioavailability of LFT-MMs compared to the original form of lenvatinib. These findings suggest that LFT-MMs are promising formulations for lenvatinib oral delivery.