HT21
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 s 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. In addition, the chemical structure of phospholipids, such as tail lengths and charge number, or the fraction of a cosurfactant, for instance cholesterol, is expected to largely influence the ability to form mixed micelles.
The aim of this project is to study mixtures of bile salt surfactant, phospholipid and cholesterol to investigate the role of cholesterol content 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 some different mole fractions of cholesterol. 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.
Farmaceutisk kemi
Fysikalisk kemi
Laborativ studie
Institutionen för läkemedelskemi, UU
UPPSALA
Magnus Bergström
magnus.bergstrom@ilk.uu.se
30hp
1