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Self-assembled phospholipid-based mixed micelles for improving the solubility, bioavailability and anticancer activity of lenvatinib.
- Source :
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Colloids & Surfaces B: Biointerfaces . May2021, Vol. 201, pN.PAG-N.PAG. 1p. - Publication Year :
- 2021
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Abstract
- [Display omitted] • The optimal LFT-MMs presented prominent enhancement in LFT solubility by 500-fold. • LFT-MMs remain stable for at least 1 month at 4 °C. • LFT-MMs rarely adsorbed proteins, and presented insignificant hemolytic rate. • LFT-MMs enhanced inhibitory activity against two main kinds of DTC cell lines. • The relative bioavailability compared with the original form of LFT was 176.7 %. 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 09277765
- Volume :
- 201
- Database :
- Academic Search Index
- Journal :
- Colloids & Surfaces B: Biointerfaces
- Publication Type :
- Academic Journal
- Accession number :
- 149734264
- Full Text :
- https://doi.org/10.1016/j.colsurfb.2021.111644