Institute of Food Science and Technology, National Taiwan University, Taipei 10617, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan; Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan. Electronic address: [Email]
5-Demethyltangeretin (5-DTAN), a polymethoxylated flavone found in citrus peels, exhibits highly potent anti-cancer activity. However, 5-DTAN is a hydrophobic compound with poor aqueous solubility, which limits its oral bioavailability and efficacy. In this study, we aimed to develop and characterize an optimal self-microemulsifying delivery system (SMEDS) formulated for 5-DTAN and to assess its anticancer activity in a xenograft model. SMEDS is a lipid-based formulation and typically comprises oil, surfactant, and co-surfactant. The results from our solubility and compatibility test revealed that ethyl oleate and d-limonene were appropriate for use as an oil phases. The optimal formulation comprised ethyl oleate/d-limonene (10%/5%), Cremophor® EL (59.5%), and PEG 400 (25.5%). With this optimal formulation, the mean particle size was 97.1 ± 6.50 nm with the highest 5-DTAN loading (3.01 ± 0.38 mg/mL) determined by photon correlation spectroscopy. The transmission electron microscopy (TEM) morphology of 5-DTAN microemulsion droplets demonstrated a spherical shape and uniform size. Our findings suggest that using 5-DTAN loading SMEDS is an effective approach for inhibiting tumor growth in colon cancer xenograft mice. In summary, this study is the first to successfully demonstrate that oral administration of 5-DTAN-loaded SMEDS serves as a promising nutraceutical for cancer prevention.