Deoxycholate-TPGS mixed nanomicelles for encapsulation of methotrexate with enhanced in vitro cytotoxicity on breast cancer cell lines

Abstract

Biocompatible mixed nanomicelles consisting of sodium deoxycholate and d-α-tocopheryl polyethylene glycol 1000 succinate have been prepared in different molar ratios (100:0, 75:25, 50:50, 25:75 and 0:100) in order to improve the aqueous solubility and in vitro anti-tumor activity of methotrexate. The nanomicelles loaded with methotrexate were prepared without using any organic solvents and characterized in terms of critical micellar concentration, particle size and drug solubilization capacity of the micellar dispersion. The optimized formulation (ratio 25:75) exhibited a spherical shape and a particle size of about 8 nm. The results of the in vitro release assay showed that the micellar system presented a sustained release behaviour compared to the solution of methotrexate. Cell viability studies in MCF-7 and MDA-MB-231 cells revealed that mixed micelles achieved lower IC50 values, in comparison to methotrexate and pralatrexate solutions. The formulated system showed a significant increase in the methotrexate cellular uptake, when compared to the free drug in both cell lines. Furthermore, hemolytic assay confirmed that methotrexate-loaded mixed micelles are compatible with red blood cells. Therefore, the mixed micelles developed in this study might be a potential nano-drug delivery system capable of overcoming in vitro resistance to methotrexate in breast cancer cells.