Preparation and evaluation of self-microemulsifying delivery system containing 5-demethyltangeretin on inhibiting xenograft tumor growth in mice
Journal
International Journal of Pharmaceutics
Journal Volume
579
Date Issued
2020
Author(s)
Abstract
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. ? 2020 Elsevier B.V.
Subjects
5-Demethyltangeretin (5-DTAN); Colon cancer; Self-microemulsifying delivery system (SMEDS)
SDGs
Other Subjects
5 demethyltangeretin; antineoplastic agent; cremophor; limonene; oil; oleic acid ethyl ester; unclassified drug; antineoplastic agent; flavone derivative; gardenin B; oleic acid; surfactant; animal experiment; animal model; animal tissue; antineoplastic activity; Article; cancer inhibition; cancer prevention; controlled study; drug delivery system; drug formulation; drug solubility; human; human cell; loading drug dose; male; microemulsion; mouse; nonhuman; particle size; photon correlation spectroscopy; priority journal; transmission electron microscopy; tumor xenograft; animal; chemistry; colon tumor; drug screening; emulsion; HT-29 cell line; medicinal chemistry; oral drug administration; pathology; Administration, Oral; Animals; Antineoplastic Agents, Phytogenic; Chemistry, Pharmaceutical; Colonic Neoplasms; Drug Delivery Systems; Emulsions; Flavones; HT29 Cells; Humans; Limonene; Male; Mice; Oleic Acids; Particle Size; Surface-Active Agents; Xenograft Model Antitumor Assays
Type
journal article