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Published on: November 1, 2017
Palm oil nanoemulsion enhances tocotrienol stability, antioxidant, and selective anti-melanoma activity
Ahmad Fariduddin Aththar1, Farhana Raushani2, Fransiska Christydira Sekaringtyas3
1Department of Biology, Faculty of Mathematics and Natural Sciences, University of Brawijaya, Malang, East Java, Indonesia.
Abstract:
Tocotrienols (T3) have been known to have potential cytotoxic activity against cancer cells. However, their ability to effectively target cancerous tissue is hampered by their lipophilic characteristics and poor bioavailability. In this study, encapsulating T3 into nanoemulsions (NE) prepared from palm oil (5-20%) and Tween-80 (3-7%) assisted with ultrasonication (5-20 min) resulted in improved stability of NE-T3 (kinetic, thermodynamic, long-term storage) and biological activity. Response Surface Methodology with Box-Behnken Design predicted the significant effect of palm oil concentrations on nanosized particle formation, while Tween-80 concentration and ultrasonication time had minimal effect on particle size. The optimum formulation achieved nanoscale characteristics of NE-T3, including a mean particle size of 64.8 ± 8 nm, polydispersity index of 0.288, and ζ-potential of - 19.16 mV, with only 5.2 ± 0.8% size variation after 60-day storage at 40 °C. It also demonstrated condition-specific thermodynamic stability, long-term storage capability, controlled drug release properties (77.97 ± 4.41% cumulative release over 54 h), and significantly enhanced antioxidant activity. The antioxidant activity (ABTS and DPPH) of NE-T3 showed IC50 values of 26.63 ± 1.8 µg/mL (ABTS) and 9.38 ± 1.24 µg/mL (DPPH), representing 1.5-2.0-fold improvement over free form of T3. The NE-T3 significantly enhanced cytotoxicity (IC50 45.07 ± 4.84 µg/mL) compared to free-T3 (IC50 78.75 ± 4.68 µg/mL) in B16F0 melanoma cells, while both showed minimal toxicity on normal NIH-3T3 cells (IC50 > 230 µg/mL). Additional anticancer assays revealed that NE-T3 induced 12.83 ± 2.1% late apoptosis and caused G1 phase cell cycle arrest. This study highlights the potential of NE-T3 as a promising platform for r combinatory cancer therapies.
Insights
Tocotrienols (T3) encapsulated in nanoemulsions (NE) show improved stability and bioavailability for cancer therapy. This NE-T3 formulation enhanced cytotoxicity against melanoma cells and induced apoptosis, showing promise for cancer treatment.
Area of Science:
- Nanotechnology
- Materials Science
- Pharmacology
Background:
- Tocotrienols (T3) exhibit potential anticancer properties but suffer from poor bioavailability.
- Lipophilic nature of T3 hinders effective targeting of cancerous tissues.
- Nanoemulsion (NE) technology offers a strategy to improve T3 delivery and efficacy.
Purpose of the Study:
- To develop and characterize T3-loaded nanoemulsions (NE-T3) using palm oil and Tween-80.
- To evaluate the stability, antioxidant activity, and anticancer efficacy of NE-T3.
- To investigate the mechanism of NE-T3-induced cancer cell death.
Main Methods:
- Nanoemulsions (NE) were prepared using palm oil, Tween-80, and ultrasonication.
- Response Surface Methodology (RSM) with Box-Behnken Design optimized NE formulation.
- Particle size, polydispersity index, and zeta potential were analyzed.
- Stability was assessed under various storage conditions.
- In vitro antioxidant activity (ABTS, DPPH) and cytotoxicity assays (B16F0 melanoma, NIH-3T3 fibroblasts) were performed.
- Apoptosis and cell cycle arrest were evaluated using flow cytometry.
Main Results:
- Optimized NE-T3 formulation achieved nanoscale characteristics (64.8 nm particle size, 0.288 PDI, -19.16 mV ζ-potential).
- NE-T3 exhibited excellent kinetic, thermodynamic, and long-term storage stability.
- Enhanced antioxidant activity (1.5-2.0-fold improvement) and controlled drug release were observed.
- NE-T3 demonstrated significantly higher cytotoxicity against B16F0 melanoma cells (IC50 45.07 µg/mL) compared to free T3 (IC50 78.75 µg/mL).
- NE-T3 induced late apoptosis (12.83%) and G1 phase cell cycle arrest in cancer cells.
- Minimal toxicity was observed in normal NIH-3T3 cells.
Conclusions:
- Nanoemulsion encapsulation significantly improves T3 stability, bioavailability, and anticancer efficacy.
- NE-T3 is a promising drug delivery system for enhancing cancer therapy.
- The findings support the potential of NE-T3 for combinatory cancer treatments.
