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Avocado (Persea americana Mill.; Lauraceae) seed-derived polyhydroxylated fatty alcohols (PFAs) or polyols (i.e., avocadene and avocadyne) are metabolic modulators that selectively induce apoptosis of leukemia stem cells and reverse pathologies associated with diet-induced obesity. Delivery systems containing avocado polyols have not been described. Herein, natural surface active properties of these polyols are characterized and incorporated into self-emulsifying drug delivery systems (SEDDS) that rely on molecular self-assembly to form fine, transparent, oil-in-water (O/W) microemulsions as small as 20 nanometers in diameter. Mechanistically, a 1:1 molar ratio of avocadene and avocadyne (i.e., avocatin B or AVO was shown to be a eutectic mixture which can be employed as a novel, bioactive, cosurfactant that significantly reduces droplet size of medium-chain triglyceride O/W emulsions stabilized with polysorbate 80. In vitro cytotoxicity of avocado polyol-SEDDS in acute myeloid leukemia cell lines indicated significant increases in potency and bioactivity compared to conventional cell culture delivery systems. A pilot pharmacokinetic evaluation of AVO SEDDS in C57BL/6J mice revealed appreciable accumulation in whole blood and biodistribution in key target tissues. Lastly, incorporation of AVO in SEDDS significantly improved encapsulation of the poorly water-soluble drugs naproxen and curcumin. Avocados have been shown to be an exclusive source of unique long carbon chain (C 17 to C 21) polyhydroxylated fatty alcohols or polyols that possess anti-cancer, anti-inflammatory and anti-microbial properties 1-4. Previously, we demonstrated that avocatin B (AVO), a 1:1 mixture of two 17-carbon polyols (avocadyne and avocadene), target mitochondria and inhibit fatty acid oxidation (FAO) which selectively induces death in leukemia cells 5-8. More recently, avocadyne has been shown to exert potent immunomodulatory effects that impede dengue virus replication in vitro 9. Furthermore, our laboratory determined that AVO inhibited FAO in skeletal muscle and pancreatic β-cells reversing insulin resistance and restoring glucose tolerance in diet-induced obesity 10. The highly promising indications for avocado polyols in human disease and nutrition necessitate the complete characterization of their physicochemical properties and subsequent development of optimal formulations for future in vivo and clinical studies. To our knowledge, use of avocado polyols is prominent in topical cosmetic formulations described briefly in patent literature 11,12. This is the first report that avocadene and avocadyne possess unique physicochemical properties ideal for SEDDS applications. SEDDS comprise a mixture of oils, co-solvents, surfactants and co-surfactants that spontaneously self-assemble into oil-in-water (O/W) or water-in-oil (W/O) nano (~100-400 nm in diameter) or micro (<100 nm in diameter) emulsions 13. Surfactants delay droplet coalescence by reducing the surface free energy associated with the oil-water interface by creating a rigid, ...