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The saponin aescin from the horse chestnut tree is a natural surfactant well-known to self-assemble as oriented-aggregates at fluid interfaces. Using model membranes in the form of lipid vesicles and Langmuir monolayers, we study the mixing properties of aescin with the phase-segregating phospholipid 1,2-dimyristoyl-sn-glycero-phosphocholine (DMPC). The binary membranes are experimentally studied on different length scales ranging from the lipid headgroup area to the macroscopic scale using small-angle X-ray scattering (SAXS), photon correlation spectroscopy (PCS), and differential scanning calorimetry (DSC) with binary bilayer vesicles and Langmuir tensiometry (LT) with lipid monolayers spread on the surface of aescin solutions. The binary interaction was found to strongly depend on aescin concentration in two well differentiated concentration regimes. Below 7 mol %, the results reveal phase segregation of nanometer-sized aescin-rich domains in an aescin-poor continuous bilayer. Above this concentration, aescin-aescin interactions dominate, which inhibit vesicle formation but lead to the formation of new membrane aggregates of smaller sizes. From LT studies in monolayers, the interaction of aescin with DMPC was shown to be stronger in the condensed phase than in the liquid expanded phase. Furthermore, a destructuring role was revealed for aescin on phospholipid membranes, similar to the fluidizing effect of cholesterol and nonsteroidal anti-inflammatory drugs (NSAIDs) on lipid bilayers. [ABSTRACT FROM AUTHOR]

In the present work, we study the interaction of the saponin aescin with the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen at concentrations of 1.2-2.5 mM. These amounts are higher than those usually used for medication (10-300 μM) to show possible structures and formulations for orally absorbed drug delivery systems. It is shown how the interaction of both substances, separately or together, alters the thermotropic phase behavior of the 1,2-dimyristoyl- sn-glycero-3-phosphocholine (DMPC) bilayer in the presence of different amounts of aescin, ranging from 20 μM to 1 mM. The methods of choice are differential scanning calorimetry (DSC), and additionally wide-angle (WAXS) and small-angle X-ray scattering (SAXS). We found that these two additives, aescin and ibuprofen, alter the temperature-dependent structural appearance of the DMPC membrane depending on the aescin and drug content. The presence of the saponin and the drug become visible on different length scales, i.e., ranging from a global structural change to inner-membrane interactions. DSC reveals that the drug and saponin alter the cooperativity of the DMPC phase transition in a concentration-dependent manner. Furthermore, there is a significant difference between the drug-containing compared to the drug-free systems. By WAXS, we could resolve that aescin reverses the strong impact of ibuprofen on the diffraction peak of DMPC. Both molecules interact strongly with the phospholipid headgroups. This becomes visible in a changing area per lipid and shifting phase transition to higher temperatures. SAXS experiments reveal that the addition of ibuprofen leads to major morphological changes in the phospholipid bilayer. SAXS experiments performed on representative samples do not only cover the drug-saponin interaction within the bilayer from the structural perspective but also confirm the visually observed macroscopic concentration and temperature-dependent phase behavior. Vesicular shape of extruded samples is conserved at low aescin contents. At intermediate aescin content, aggregation between vesicles occurs, whereby the strength of aggregation is reduced by ibuprofen. At high aescin contents, DMPC bilayers are solubilized. The kind of formed structures depends on temperature and drug content. At low temperature, separated bilayer sheets are formed. Their size increases with ibuprofen in a concentration-dependent manner. At high temperature, the drug-free system reorganizes into stacked sheets. Whereas sheets at 5 mol % ibuprofen close to vesicles, the ones with 10 mol % of the drug increase massively in size. Altogether, ibuprofen was found to rather enhance than inhibit structural and thermotropic membrane modifications induced by the aescin on the DMPC model membrane.