Ahmad Fariduddin Aththar, Farhana Raushani, Fransiska Christydira Sekaringtyas, Sjaikhurrizal El Muttaqien, Damai Ria Setyawati, Riyona Desvy Pratiwi, Muhaimin Rifa’i, Siti Irma Rahmawati, Masteria Yunovilsa Putra, Peni Ahmadi, Dwi Wahyu Indriani, Janet Tan Sui Ling, Endrika Widyastuti, Asep Bayu, A’liyatur Rosyidah
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. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2025.
Department of Biology, Faculty of Mathematics and Natural Sciences, University of Brawijaya, East Java, Malang, Indonesia; Department of Biotechnology, Faculty of Agricultural Technology, University of Brawijaya, East Java, Malang, Indonesia; Research Center for Radioisotope, Radiopharmaceutical, and Biodosimetry Technology, Research Organization for Nuclear Energy, National Research and Innovation Agency (BRIN), Banten, South Tangerang, Indonesia; Research Center of Vaccine and Drugs, Research Organization for Health, National Research and Innovation Agency (BRIN), West Java, Bogor, Indonesia; Faculty of Pharmacy, Universitas Indonesia, West Java, Depok, Indonesia; Department of Pharmaceutical Technology, Faculty of Pharmacy, Universiti Malaya, Kuala Lumpur, Malaysia
