Bioflavonoid Fisetin Loadedα-Tocopherol-Poly(lactic acid)-Based Polymeric Micelles for Enhanced Anticancer Efficacy in Breast Cancers.
Pharm Res. 2017 Feb ;34(2):453-461. Epub 2016 Dec 21. PMID: 28004315
PURPOSE: In this study, tocopherol based polymeric micelles were successfully prepared to enhance the anticancer effect of fisetin (FIS) in breast cancer cells.
METHODS: The drug-loaded carrier was characterized in terms of physicochemical and in vivo parameters.
RESULTS: Compared to FIS, FIS-TPN showed higher cellular uptake in MCF-7 breast cancer cells as revealed by CLSM and flow cytometry. The cytotoxicity assay results clearly showed that the free FIS and FIS-TPN exhibited a typical dose-dependent toxic effect in MCF-7 breast cancer cells. Especially, enhanced cytotoxic effect of FIS was observed when loaded in a nanocarrier. Free FIS induced a ~11% apoptosis whereas FIS-TPN induced a significantly greater apoptosis of ~20% by the end of 24 h. At 48 h, similar trend continued and free FIS showed ~30% of apoptosis whereas ~42% cell apoptosis was observed in FIS-TPN treated group. Notably, migration of cancer cell was significantly inhibited when treated with FIS-TPN formulations. The FIS-TPN significantly reduced to tumor burden andH&E staining showed the lowest tumor volume and higher cell apoptosis.
CONCLUSIONS: All the findings suggest that the fisetin-loaded TPGS-PLA polymeric micelles serve as a potential candidate and promising alternative for the effective treatment of breast cancers.