SIMVASTATIN LOADED NANO MIXED MICELLES: AN APPROACH TO TREAT HORMONE DEPENDENT CARCINOMAS

The main objective of the present research was to develop mixed micelles using two biocompatible copolymers, D-α-tocopheryl polyethylene-glycol 1000 succinate (TPGS) and poloxamer 188 (P188) to improve the aqueous solubility and targeting efficacy of Simvastatin (SMV) against a variety of hormone-dependent cancers. A solvent evaporation technique prepared the plain/single copolymer micelles (SCMs) and mixed micelles (MMs). The prepared SCMs and MMs were characterized for critical micelle concentration (CMC), SMV content, particle size by dynamic light scattering (DLS), surface morphology by transmission electron microscopy (TEM), in-vitro SMV release and hemolysis. The SCMs and MMs showed mean particle size of 98 ± 5 nm and 129 ± 6 nm, respectively. SCMs showed SMV loading of 79.7 ± 5.6% while MMs exhibited improved SMV loading of 94.5 ± 6.5. The developed MMs system showed significantly lower CMC (3.5 fold less) than SCMs revealing their higher in-vivo stability. Moreover, SCMs and MMs exhibited zero order release profile, lower hemolytic behavior (<5% of hemolysis), when compared to plain SMV solution. The in-vitro cytotoxicity assay was conducted on MCF-7 (human breast cancer) cell line. Cytotoxicity studies revealed significantly improved antitumor activity of MMs when compared to SCMs and plain SMV after both incubation time points (24 and 48 h). In conclusion, the developed SMV-loaded MMs could improve the targeting and therapeutic efficacy of loaded SMV against hormone-dependent breast, prostate and ovarian carcinomas. Besides, this approach could be a potential alternative for development. However, further studies are needed to ascertain these facts.