A remarkable in vitro cytotoxic, cell cycle arresting and proapoptotic characteristics of low-dose mixed micellar simvastatin combined with alendronate sodium

The objective of the present study was to screen the effect of increased simvastatin (SVS) solubility, through mixed micelles as a model approach, on in vitro anticancer efficacy in combination with hydrophilic alendronate sodium (ADS) as a strategy to improve therapeutic efficacy and to repositioning the existing drugs. The SVS-loaded mixed micelles (SVS-MMs) composed of TPGS and Poloxamer-407 were prepared using the film dispersion method and characterized for SVS loading and mean particle size. The optimized SVS-MMs were physically mixed with plain ADS (SVS + ADS MMs) and screened for in vitro cytotoxicity using MTT assay and cell cycle arresting and apoptotic activities using FACS technique. The optimized SVS-MMs showed maximum SVS loading (97.3 +/- 2.3%) with minimum particle size (206 +/- 8 nm). The SVS + ADS MM treatment significantly (P < 0.001) inhibited the cell growth with low IC50 values against all cells (A549: 0.037 +/- 0.028 mu g/mL, MDAMB-231: 0.172 +/- 0.031 mu g/mL, PC-3: 0.022 +/- 0.015 mu g/mL). Further, the SVS + ADS MM treatment significantly inhibited the cell multiplication in the S phase and resulted in high % of late apoptotic and necrotic cells at low concentration (0.05 and 0.15 mu g/mL) as compared other test samples. The above results revealed the significance of encapsulating SVS in the core of MMs (improved solubility), and high efficacy and quick effect of SVS + ADS MM treatment against all cell lines screened.