Tocotrienol Nanoemulsion Platform of Curcumin Elicit Elevated Apoptosis and Augmentation of Anticancer Efficacy against Breast and Ovarian Carcinomas

Vitamin E (VE) tocotrienols (T3), recognized for their cancer-specific anti-proliferative and pro-apoptotic activities, have been previously fabricated into bio-active nanoemulsion (NE) formulations. Here, our viscosity-adapted delta-T3 NE platform was developed to additionally incorporate curcumin (CUR), which is known for its potent suppression of signaling pathways involved in malignant cell growth, survival and metastasis. Thanks to efficient 70: 30 wt % surfactant mix of Lutrol F-127: VE-TPGS, in conjunction with optimal CUR loading, a prototype CUR in delta-T3 NE was successfully prepared. Model CUR/delta-T3 NE demonstrated excellent nano-scale aspects (mean particle size = 261 nm, PDI = 0.27, and zeta-potential = 35 mV), pharmaceutical stability, and controlled release properties. Suitability for systemic administration was also verified via standardized in vitro biocompatibility and hemocompatibility assays. In two human cancer cells (MCF-7 and OVCAR-8), our CUR/delta-T3 NE prominently suppressed constitutive NF-kappa B activation, and significantly induced apoptosis. Finally, the combined CUR/delta-T3 NE produced superior cytotoxicity profiles, in concentration-and time-dependent manners (p <= 0.05), at least three to four folds lower IC50 than in closest CUR control. The strong synergism, estimated in both cultured carcinomas, revealed the augmented therapeutic efficacy of our CUR/delta-T3 NE combined platform, supporting its strong potential towards pharmaceutical development for cancer therapy.