A new family of hydroxytyrosol phenolipids for the antioxidant protection of liposomal systems

Abstract

Hydroxytyrosol (HT) is a well-known olive oil polyphenol for its high antioxidant capacity and important cardio and neuroprotective effects. However, its use in lipidic systems is limited, due to its hydrophilic character. In this study, we approach the particular structure of xanthophylls and synthetize HT esters specially designed for the protection of liposomal systems. These HT esters contain two polyphenolic moieties separated by a lipophilic alkyl spacer of different length (12, 16 or 22 carbons). To evaluate the antioxidant activity of these compounds against the 2,2'-azobis(2-amidinopropane) hydrochloride induced oxidation, soybean phospholipid liposomes were used. Fluorescence quenching studies were used to assess the insertion of the compounds in the liposomes. The synthetized HT derivatives were able to protect liposomes from induced oxidation when added to the suspensions. The rank of activity was severely influenced by the alkyl chain length of the spacer molecule, being the C12 derivative the most active antioxidant, with an increase in the oxidative stability of liposomes of 2.2 times when compared with the control. The incorporation of compounds during liposome preparation improved the antioxidant capacity of all HT derivatives by about 2.8 times, when compared to the control. This is probably due to a similar transmembrane position with both polyphenolic rings located at the phospholipid polar heads. The synthesis of bis-ester derivatives seems to be a promising strategy to fine-tune antioxidant molecules at biomembranes, thus increasing the oxidative stability of liposomal systems by improving the antioxidant activity of hydrophilic phenolic compounds with high free radical scavenging activity.