Improving intracellular uptake of 5-demethyltangeretin by food grade nanoemulsions

- Food grade oil-in-water emulsions with different droplet sizes were manufactured.
- The effects of emulsions on cellular update of 5-demethyltangeretin were determined.
- The emulsion with smaller droplet size led to higher cellular uptake.
- The emulsion with smaller droplet size led to stronger inhibition on cancer cells.

5-Demethyltangeretin (5DT) is a unique citrus flavonoid that has been shown to have anti-cancer effects, but its low water-solubility and poor oral bioavailability may limit its application as a nutraceutical. In this study, we utilized emulsion-based delivery systems to increase the bioavailability of 5DT and its uptake by intestinal cancer cells. Oil-in-water emulsions with different mean droplet radii (r = 67, 125 and 203 nm) were fabricated using high-pressure homogenization. The amount of 5DT absorbed by intestinal cancer cells was quantified by HPLC using an electrochemistry detector. The relative percentages of 5DT absorption compared to a reference emulsion (r = 67 nm) were: 5.9% (in water, crystal); 13.1% (in medium chain triglyceride (MCT), crystal); 30.6% (emulsion, r = 203 nm); and 92.9% (emulsion, r = 125 nm). A cytotoxicity assay showed that 5DT encapsulated in smaller droplets produced stronger growth inhibition than those in larger droplets, and much higher than those dispersed in bulk MCT or bulk water. 5DT encapsulated within emulsions with small droplet sizes (nanoemulsions) produced higher cellular absorption and lower cancer cell viability. Our results suggested that this type delivery system may be useful for the application of 5DT and other similar nutraceuticals in functional foods and beverages.