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Int. J. Mol. Sci. 2016, 17(11), 1792; doi:10.3390/ijms17111792

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

1
Department of Pharmaceutical Sciences/Nanomedicine Center of Excellence in Translational Cancer Research (Nanomedicine COE-TCR), College of Pharmacy-Glendale, Midwestern University, Glendale Hall 236-14, 19555 N. 59th Ave., Glendale, AZ 85308, USA
2
Arizona College of Osteopathic Medicine, Midwestern University, 19555 N. 59th Ave., Glendale, AZ 85308, USA
3
Department of Biomedical Sciences, College of Health Sciences, Midwestern University, 19555 N. 59th Ave., Glendale, AZ 85308, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Maria Laura Colombo, Laura Di Renzo and Rafat A. Siddiqui
Received: 4 September 2016 / Revised: 19 October 2016 / Accepted: 20 October 2016 / Published: 26 October 2016
(This article belongs to the Special Issue Tocopherols and Tocotrienols: Metabolism and Properties)
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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 δ-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 δ-T3 NE was successfully prepared. Model CUR/δ-T3 NE demonstrated excellent nano-scale aspects (mean particle size = 261 nm, PDI = 0.27, and ζ-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/δ-T3 NE prominently suppressed constitutive NF-κB activation, and significantly induced apoptosis. Finally, the combined CUR/δ-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/δ-T3 NE combined platform, supporting its strong potential towards pharmaceutical development for cancer therapy. View Full-Text
Keywords: tocotrienols; tocopherols; polyphenols; nanoemulsion; antiproliferative; biocompatibility; apoptosis; tumor necrosis factor-α; caspase tocotrienols; tocopherols; polyphenols; nanoemulsion; antiproliferative; biocompatibility; apoptosis; tumor necrosis factor-α; caspase
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Steuber, N.; Vo, K.; Wadhwa, R.; Birch, J.; Iacoban, P.; Chavez, P.; Elbayoumi, T.A. Tocotrienol Nanoemulsion Platform of Curcumin Elicit Elevated Apoptosis and Augmentation of Anticancer Efficacy against Breast and Ovarian Carcinomas. Int. J. Mol. Sci. 2016, 17, 1792.

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