Phospholipid molecules self-assemble to form bilayers that are poorly soluble in an aqueous solvent. Phospholipids may, however, be readily dissolved by mixing with a bile salt or amphiphilic drug surfactant that forms mixed surfactant/phospholipid micelles. Mixed bile salt/phospholipid micelles play an important role in the digestion of fats in the gastrointestinal tract as well as solubilizers of water-insoluble drugs and other drug delivery applications. The ability of surfactants to dissolve phospholipids largely depends on the chemical structure of both surfactant and phospholipid. While bile salt and amphiphilic drug surfactants, with a rigid chemical structure, are good solubilizers of phospholipids, conventional surfactants, with a flexible aliphatic hydrocarbon tail, are poor solubilizers.
Bile salts are very sensitive to temperature, which seems to influence the spontaneous curvature of the surfactants. The aim of this project is to study a particular bile salt surfactant/phospholipid mixture to investigate the role of temperature on the solubilization of phospholipid bilayers and formation of mixed micelles. The phospholipid content (mole fraction) at the transition from bilayers to micelles will be determined for at different temperatures. The size, shape and structure of micelles (globular, rod-like or thread-like micelles) and bilayer aggregates (vesicles or disks) that are formed will be determined with static and dynamic light scattering (SLS and DLS). Complementary techniques such as surface tension, small-angle x-ray scattering (SAXS), electron microscopy and time-resolved fluorescence quenching may as well be considered.
Institutionen för läkemedelskemi, UU