Tocotrienol nanoemulsion platform of curcumin elicit elevated apoptosis and augmentation of anticancer efficacy against breast and ovarian carcinomas

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Abstract

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-kappaB 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.

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Steuber, N., Vo, K., Wadhwa, R., Birch, J., Iacoban, P., Chavez, P., & Elbayoumi, T. A. (2016). Tocotrienol nanoemulsion platform of curcumin elicit elevated apoptosis and augmentation of anticancer efficacy against breast and ovarian carcinomas. International Journal of Molecular Sciences, 17(11). https://doi.org/10.3390/ijms17111792

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