Flavonoid-biomembrane interactions: a calorimetric study on dipalmitoylphosphatidylcholine vesicles

Flavonoids, a group of naturally occurring benzo-gamma-derivatives, have been shown to possess several biological properties, many of which may be related, partially at least, to their capacity to penetrate into the cell membrane and so to affect membrane-dependent processes. In the present paper we report the results of an investigation by differential scanning calorimetry (DSC) on the effects of three flavonoids (quercetin, hesperetin and naringenin) upon the gel-to-liquid crystalline phase transition of model membranes constituted by L-alpha-dipalmitoylphosphatidylcholine (DPPC) vesicles. All tested flavonoids interacted with DPPC liposomes causing different shifts, towards lower values, of the T-m typical for DPPC multilayers; the enthalpy changes (Delta H), related to the calorimetric peak area, remained nearly constant. Furthermore, their effects on DPPC thermotropic behaviour were greater for high molar concentrations (up to a limit value different for each flavonoid) and were affected by the time. Several hypotheses (drug molecule aggregation into the model membrane, changes in the barrier function of the lipid bilayer, different drug structural features and conformation, possible formation of flavonoid-phospholipid complexes) are presented to explain the nature of the interaction between flavonoids and phospholipid vesicles.