The potential of hydroxytyrosol fatty acid esters to enhance oral bioavailabilities of hydroxytyrosol and fatty acids: Continuous and slow-release ability in small intestine and blood

•HTy-Es could be hydrolyzed by pancreatic lipase in small intestine.•HTy-Es could be hydrolyzed by carboxylesterase in blood.•HTy-Es showed slow-release of hydroxytyrosol (HTy) and fatty acid (FA).•Such two-step release of HTy and FA may improve their oral bio-availabilities.•Controllable release rate will be achieved from different chain length and isomers. HPLC-UV analysis in rat everted gut sac and in vitro simulated digestion models indicated that hydroxytyrosol fatty acid esters (HTy-Es) could be hydrolyzed by pancreatic lipase to slow-release of free fatty acids (FAs) and HTy. Meanwhile, the HTy-Es, the liberated FAs and the HTy could cross the membrane and were transported into blood circulation. HTy-Es were further hydrolyzed by carboxylesterase in in vitro rat plasma hydrolysis model, which also showed slow-release of FAs (C1-C4) and HTy. Especially, the rates of hydrolysis and transport initially increased and then decreased with the increasing alkyl chain length. Besides, the above rates of the HTy-Es with a straight chain were greater than those of its isomer with a branched chain. Therefore, the above-mentioned continuous and slow-release of FAs and HTy in small intestine and blood clearly demonstrated that HTy-Es would be an effective approach to enhance oral bioavailabilities of free fatty acids and hydroxytyrosol.