Encapsulation of naturally occurring flavonoids into liposomes: physicochemical properties and biological activity against human cancer cell lines

Abstract

Liposomes consisting of egg phosphatidylcholine were prepared by a thin-film hydration method followed by sonication and were used to investigate the percentage encapsulation of four flavonoids (quercetin, rutin, isoscutellarein and isoscutellarein diglycoside). The lipid recovery and the flavonoid-to-lipid molar ratio were measured using high-performance thin-layer chromatography/flame ionization detection and UV-vis spectroscopy. Differential scanning calorimetry was used to study the effect of the flavonoids on the phase transition temperature and on the enthalpy of the main phase transition of dipalmitoylphosphatidylcholine bilayers, and their ability to influence the membrane fluidity. The final liposomal formulation incorporating flavonoids, as well as free flavonoids, were tested for their activity against human cancer cell lines using the sulforhodamine B assay. The results showed that the encapsulation efficiency varied from 95% (0.21 flavonoid-to-lipid molar ratio) to 37.5% (0.09 flavonoid-to-lipid molar ratio) for isoscutellarein and its glycoside, respectively. The differential scanning calorimetry data showed close thermal and dynamic effects depending on the structure of the flavonoids, and suggest that there is a relationship between flavonoid molecular structure and the interaction with model membranes. Liposomal isoscutellarein showed improved growth inhibiting activity against all cell lines tested in comparison with that of its free form, which was inactive (>100 μM).