Nanoemulsion-Enabled Oral Delivery of Novel Anticancer ω-3 Fatty Acid Derivatives

Lipid-based drugs are emerging as an interesting class of novel anticancer drugs with the potential to target specific cancer cell metabolic pathways linked to their proliferation and invasiveness. In particular, omega-3 polyunsaturated fatty acids (PUFA) derivatives such as epoxides and their bioisosteres have demonstrated the potential to suppress growth and promote apoptosis in triple-negative human breast cancer cells MDA-MB-231. In this study, 16-(4'-chloro-3'-trifluorophenyl)carbamoylamino]hexadecanoic acid (ClFPh-CHA), an anticancer lipid derived from omega-3,17,18-epoxyeicosanoic acid, was formulated as a stable nanoemulsion with size around 150 nm and narrow droplet size distribution (PDI < 0.200) through phase-inversion emulsification process followed by high pressure homogenization in view of an oral administration. The ClFPh-CHA-loaded nanoemulsions were able to significantly decrease the relative tumor volume in mice bearing an intramammary tumor xenograft at all doses tested (2.5, 10 and 40 mg/kg) after 32 days of daily oral administration. Furthermore, absolute tumor weight was decreased to 50% of untreated control at 10 and 40 mg/kg, while intraperitoneal administration could achieve a significant reduction only at the highest dose of 40 mg/kg. Results suggest that oral administration of ClFPh-CHA formulated as a nanoemulsion has a sufficient bioavailability to provide an anticancer effect in mice and that the activity is at least equal if not superior to that obtained by a conventional parenteral administration of equivalent doses of the same drug.