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Int J Mol Sci. 2016 Oct 26;17(11). pii: E1792.

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

Author information

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. njsteuber@gmail.com.
2
Arizona College of Osteopathic Medicine, Midwestern University, 19555 N. 59th Ave., Glendale, AZ 85308, USA. kvo95@midwestern.edu.
3
Arizona College of Osteopathic Medicine, Midwestern University, 19555 N. 59th Ave., Glendale, AZ 85308, USA. rwadhwa96@midwestern.edu.
4
Arizona College of Osteopathic Medicine, Midwestern University, 19555 N. 59th Ave., Glendale, AZ 85308, USA. jordan.birch1@gmail.com.
5
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. piacob@midwestern.edu.
6
Department of Biomedical Sciences, College of Health Sciences, Midwestern University, 19555 N. 59th Ave., Glendale, AZ 85308, USA. pchave@midwestern.edu.
7
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. telbayoumi@midwestern.edu.

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.

KEYWORDS:

antiproliferative; apoptosis; biocompatibility; caspase; nanoemulsion; polyphenols; tocopherols; tocotrienols; tumor necrosis factor-α

PMID:
27792193
PMCID:
PMC5133793
DOI:
10.3390/ijms17111792
[Indexed for MEDLINE]
Free PMC Article

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