title: Tocotrienol Nanoemulsion Platform of Curcumin Elicit Elevated Apoptosis and Augmentation of Anticancer Efficacy against Breast and Ovarian Carcinomas.
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 IC50than 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.
authors: 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.
authors: Nelson
authors: N
authors: Steuber
authors: Arizona College of Osteopathic Medicine, Midwestern University, 19555 N. 59th Ave., Glendale, AZ 85308, USA. kvo95@midwestern.edu.
authors: Kathy
authors: K
authors: Vo
authors: Arizona College of Osteopathic Medicine, Midwestern University, 19555 N. 59th Ave., Glendale, AZ 85308, USA. rwadhwa96@midwestern.edu.
authors: Ritambhara
authors: R
authors: Wadhwa
authors: Arizona College of Osteopathic Medicine, Midwestern University, 19555 N. 59th Ave., Glendale, AZ 85308, USA. jordan.birch1@gmail.com.
authors: Jordan
authors: J
authors: Birch
authors: 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.
authors: Paulina
authors: P
authors: Iacoban
authors: Department of Biomedical Sciences, College of Health Sciences, Midwestern University, 19555 N. 59th Ave., Glendale, AZ 85308, USA. pchave@midwestern.edu.
authors: Pedro
authors: P
authors: Chavez
authors: 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.
authors: Tamer A
authors: TA
authors: Elbayoumi
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001940:Breast / Q000187:drug effects / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage / Q000627:therapeutic use*; D003692:Delayed-Action Preparations / Q000737:chemistry; D004655:Emulsions / Q000737:chemistry; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010053:Ovary / Q000187:drug effects / Q000473:pathology; D024508:Tocotrienols / Q000008:administration & dosage / Q000627:therapeutic use*; D014815:Vitamins / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004655:Emulsions; D024508:Tocotrienols; D014815:Vitamins; D003474:Curcumin
keywords: antiproliferative; apoptosis; biocompatibility; caspase; nanoemulsion; polyphenols; tocopherols; tocotrienols; tumor necrosis factor-α