Dissolution mechanism of supported phospholipid bilayer in the presence of amphiphilic drug investigated by neutron reflectometry and quartz crystal microbalance with dissipation monitoring.

The influence and interaction of the ionizable amphiphilic drug amitriptyline hydrochloride (AMT) on a 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) phospholipid bilayer supported on a silica surface have been investigated using a combination of neutron reflectometry and quartz crystal microbalance with dissipation monitoring. Adding AMT solutions with concentrations 3, 12, and 50 mM leaves the lipid bilayer mainly intact and we observe most of the AMT molecules attached to the head-group region of the outer bilayer leaflet. Virtually no AMT penetrates into the hydrophilic head-group region of the inner leaflet close to the silica surface. By adding 200 mM AMT solution, the lipid bilayer dissolved entirely, indicating a threshold concentration for the solubilization of the bilayer by AMT. The observed threshold concentration is consistent with the observation that various bilayer structures abruptly transform into mixed AMT-DOPC micelles beyond a certain AMT-DOPC composition. Based on our experimental observations, we suggest that the penetration of drug into the phospholipid bilayer, and subsequent solubilization of the membrane, follows a two-step mechanism with the outer leaflet being removed prior to the inner leaflet.

Correlation between the geometrical shape and growth behaviour of surfactant micelles investigated with small-angle neutron scattering.

The correlation between the growth behaviour and geometrical shape for CTAB-rich mixed micelles formed by the cationic surfactant hexadecyl trimethyl ammonium bromide (CTAB) and the anionic surfactant sodium octyl sulphate (SOS) has been investigated with small-angle neutron scattering (SANS). Small tablet-shaped micelles formed by CTAB are found to grow only weakly in size with increasing surfactant concentration. The extent of growth becomes increasingly stronger as the fraction of SOS is increased. At higher fractions of SOS, a rather weak growth at low surfactant concentrations is followed by a sharp increase in aggregation numbers beyond a certain surfactant concentration. Such an abrupt transition from weakly to strongly growing micelles has been observed in the past for several micellar systems and is usually referred to as the second critical micelle concentration. The growth behaviour has been rationalized from a theoretical point of view by means of employing the recently developed general micelle model. The theory excellently predicts micellar growth behaviours as well as the observed correlation between the geometrical shape and micellar growth. In accordance, both width and length are found to slightly increase for weakly growing tablet-shaped micelles. On the other hand, strongly growing micelles that are observed above the second cmc display a completely different behaviour, according to which the length increases considerably while the width of the micelles decreases. Most interestingly, by means of optimizing the agreement between the general micelle model and experimentally determined aggregation numbers, we are able to determine the three bending elasticity constants: spontaneous curvature, bending rigidity and saddle-splay constant.