Malaysian tocotrienol supplier Excelvite is working with supplement brands to promote the use of tocotrienol-rich vitamin E to pharmacists and doctors treating patients with diabetic kidney disease (DKD), on the back of new clinical findings.
Monthly Archives: February 2021
Stable W/O/W multiple nanoemulsion encapsulating natural tocotrienols and caffeic acid with cisplatin synergistically treated cancer cell lines (A549 and HEP G2) and reduced toxicity on normal cell line (HEK 293)
Revathi Raviadaran, Mei Han Ng, Davannendran Chandran, Kah Kooi Ooi, Sivakumar Manickam
Mater Sci Eng C Mater Biol Appl . 2021 Feb;121:111808. doi: 10.1016/j.msec.2020.111808. Epub 2020 Dec 22.
Abstract
This work aimed to evaluate the effects of encapsulated tocotrienols (TRF) and caffeic acid (CA) in water-in-oil-in-water (W/O/W) multiple nanoemulsion with cisplatin towards cancer cells. This work is important considering the limited efficacy of cisplatin due to tumour resistance, as well as its severe side effects. A549 and HEP G2 cancer cell lines were utilised for evaluating the efficacy of the encapsulated W/O/W while HEK 293 normal cell line was used for evaluating the toxicity. TRF, CA and CIS synergistically improved apoptosis in the late apoptotic phase in A549 and HEP G2 by 23.1% and 24.9%, respectively. The generation of ROS was enhanced using TRF:CA:CIS by 16.9% and 30.2% for A549 and HEP G2, respectively. Cell cycle analysis showed an enhanced cell arrest in the G0/G1 phase for both A549 and HEP G2. TRF, CA and CIS led to cell death in A549 and HEP G2. For HEK 293, ~33% cell viability was found when only CIS was used while >95% cell viability was observed when TRF, CA and CIS were used. This study demonstrates that the encapsulated TRF and CA in W/O/W with CIS synergistically improved therapeutic efficacy towards cancer cells, as well as lowered the toxicity effects towards normal cells.
Therapeutic potential of annatto tocotrienol with self-emulsifying drug delivery system in a rat model of postmenopausal bone loss
Nur-Vaizura Mohamad, Soelaiman Ima-Nirwana, Kok-Yong Chin
Biomed Pharmacother . 2021 Feb 11;137:111368. doi: 10.1016/j.biopha.2021.111368. Online ahead of print.
Abstract
Tocotrienol has been shown to prevent bone loss in animal models of postmenopausal osteoporosis, but the low oral bioavailability might limit its use. A self-emulsifying drug delivery system (SEDDS) could increase the bioavailability of tocotrienol. However, evidence of this system in improving the skeletal effects of tocotrienol is scanty. This study aims to evaluate the therapeutic efficacy of annatto tocotrienol with SEDDS in a rat model of postmenopausal bone loss. Ten-month-old female Sprague Dawley rats were randomized into six groups. The baseline group was euthanatized at the onset of the study. Four other groups underwent ovariectomy to induce estrogen deficiency. The sham underwent similar surgery procedure, but their ovaries were retained. Eight weeks after surgery, the ovariectomized rats received one of the four different regimens orally daily: (a) SEDDS, (b) annatto tocotrienol [60 mg/kg body weight (b.w.)] without SEDDS, (c) annatto-tocotrienol (60 mg/kg b.w.) with SEDDS, (d) raloxifene (1 mg/kg b.w.). After eight weeks of treatment, blood was collected for the measurement of delta-tocotrienol level and oxidative stress markers. The rats were euthanized and their bones were harvested for the evaluation of the bone microstructure, calcium content and strength. Circulating delta-tocotrienol level was significantly higher in rats receiving annatto tocotrienol with SEDDS compared to the group receiving unformulated annatto-tocotrienol (p < 0.05). Treatment with unformulated or SEDDS-formulated annatto tocotrienol improved cortical bone thickness, preserved bone calcium content, increased bone biomechanical strength and increased antioxidant enzyme activities compared with the ovariectomized group (p < 0.05). Only SEDDS-formulated annatto tocotrienol improved trabecular microstructure, bone stiffness and lowered malondialdehyde level (p < 0.05 vs the ovariectomized group). The improvement caused by annatto tocotrienol was comparable to raloxifene. In conclusion, SEDDS improves the bioavailability and skeletal therapeutic effects of annatto tocotrienol in a rat model of postmenopausal bone loss. This formulation should be tested in a human clinical trial to validate its efficacy.
An evaluation of tocotrienol ethosomes for transdermal delivery using Strat-M ® membrane and excised human skin
Rajesh Sreedharan Nair, Nashiru Billa, Chee-Onn Leong, Andrew P Morris
Pharm Dev Technol . 2021 Feb;26(2):243-251. doi: 10.1080/10837450.2020.1860087. Epub 2020 Dec 15.
Abstract
Tocotrienol (TRF) ethosomes were developed and evaluated in vitro for potential transdermal delivery against melanoma. The optimised TRF ethosomal size ranged between 64.9 ± 2.2 nm to 79.6 ± 3.9 nm and zeta potential (ZP) between -53.3 mV to -62.0 ± 2.6 mV. Characterisation of the ethosomes by ATR-FTIR indicated the successful formation of TRF-ethosomes. Scanning electron microscopy (SEM) images demonstrated the spherical shape of ethosomes, and the entrapment efficiencies of all the formulations were above 66%. In vitro permeation studies using full-thickness human skin showed that the permeation of gamma-T3 from the TRF ethosomal formulations was significantly higher (p < 0.05) than from the control. The cumulative amount of gamma-T3 permeated from TRF ethosome after 48 hours was 1.03 ± 0.24 µg cm-2 with a flux of 0.03 ± 0.01 µg cm-2 h-1. Furthermore, the flux of gamma-T3 across the Strat-M ® and the epidermal membrane was significantly higher than that across full-thickness human skin (p < 0.05). In vitro cytotoxicity studies on HaCat cells showed significantly higher cell viability than the pure drug solution (p < 0.05). The enhanced skin permeation and high cell viability associated with this formulation suggest a promising carrier for transdermal delivery.
Stabilization and Release of Palm Tocotrienol Emulsion Fabricated Using pH-Sensitive Calcium Carbonate
Phui Yee Tan, Beng Ti Tey, Eng Seng Chan, Oi Ming Lai, Hon Weng Chang, Tai Boon Tan, Yuanfa Liu, Yong Wang, Chin Ping Tan
Foods . 2021 Feb 7;10(2):358. doi: 10.3390/foods10020358.
Abstract
Calcium carbonate (CaCO3) has been utilized as a pH-responsive component in various products. In this present work, palm tocotrienols-rich fraction (TRF) was successfully entrapped in a self-assembled oil-in-water (O/W) emulsion system by using CaCO3 as the stabilizer. The emulsion droplet size, viscosity and tocotrienols entrapment efficiency (EE) were strongly affected by varying the processing (homogenization speed and time) and formulation (CaCO3 and TRF concentrations) parameters. Our findings indicated that the combination of 5000 rpm homogenization speed, 15 min homogenization time, 0.75% CaCO3 concentration and 2% TRF concentration resulted in a high EE of tocotrienols (92.59-99.16%) and small droplet size (18.83 ± 1.36 µm). The resulting emulsion system readily released the entrapped tocotrienols across the pH range tested (pH 1-9); with relatively the highest release observed at pH 3. The current study presents a potential pH-sensitive emulsion system for the entrapment and delivery of palm tocotrienols.
Co-encapsulation of gemcitabine and tocotrienols in nanovesicles enhanced efficacy in pancreatic cancer
Geetha Maniam, Chun-Wai Mai, Mohd Zulkefeli, Ju-Yen Fu
Nanomedicine (Lond) . 2021 Feb;16(5):373-389. doi: 10.2217/nnm-2020-0374. Epub 2021 Feb 5.
Abstract
Aim: To synthesize niosomes co-encapsulating gemcitabine (GEM) and tocotrienols, and physicochemically characterize and evaluate the antipancreatic effects of the nanoformulation on Panc 10.05, SW 1990, AsPC-1 and BxPC-3 cells. Materials & methods: Niosomes-entrapping GEM and tocotrienols composed of Span 60, cholesterol and D-α-tocopheryl polyethylene glycol 1000 succinate were produced by Handjani-Vila and film hydration methods. Results: The film hydration produced vesicles measuring 161.9 ± 0.5 nm, approximately 50% smaller in size than Handjani-Vila method, with maximum entrapment efficiencies of 20.07 ± 0.22% for GEM and 34.52 ± 0.10% for tocotrienols. In Panc 10.05 cells, GEM’s antiproliferative effect was enhanced 2.78-fold in combination with tocotrienols. Niosomes produced a significant ninefold enhancement in cytotoxicity of the combination, supported by significantly higher cellular uptake of GEM in the cells. Conclusion: This study is a proof of concept on the synthesis of dual-drug niosomes and their efficacy on pancreatic cancer cells in vitro.
γ-Tocotrienol reverses multidrug resistance of breast cancer cells through the regulation of the γ-Tocotrienol-NF-κB-P-gp axis
Yuedi Ding, Jun Fan, Zhenqiang Fan, Kai Zhang
J Steroid Biochem Mol Biol . 2021 May;209:105835. doi: 10.1016/j.jsbmb.2021.105835. Epub 2021 Feb 5.
Abstract
The problem of multidrug resistance (MDR) presents a major obstacle in the chemotherapy of cancer. The MDR phenotype is often linked to the overexpression of ATP-binding cassette (ABC) transporters, that pumps out and decreased intracellular drug accumulation. γ-Tocotrienol, an unsaturated tocopherol belonging to the vitamin E family, has been shown to reverse the MDR of MCF-7/Adr cell. To reveal the role of γ-tocotrienol-NF-κB-P-gp axis in the reversal process, the expression level of mdr1/P-gp was determined by real-time PCR and western blot, while NF-κB activity was detected by immunofluorescence and NF-κB transcriptional activity reporter assay. Besides, mdr1 promoter activity and P-gp transport capacity were measured with the effect of γ-tocotrienol and NF-κB agonist/antagonist. Results showed that γ-tocotrienol effectively inhibited the expression levels of mdr1 mRNA and P-gp protein. It is demonstrated that γ-tocotrienol also suppressed mdr1 promoter activity and the efflux activity of P-gp. In addition, the activation of NF-κB signaling pathway and the transcriptional activity of NF-κB were both reduced by γ-tocotrienol. Evidences also showed that the NF-κB pathway is really involved in the regulation of the expression and function of mdr1/P-gp. Taken together, we confirmed that γ-tocotrienol reversed the MDR of MCF-7/Adr through the signaling pathway of NF-κB and P-gp.