The influence of molecular structure of phospholipids on the transition from micelles to bilayers in bile salt surfactant/phospholipid mixtures

Abstract: 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. 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 influence the ability to form mixed micelles. In this paper, the aggregation behaviour and mixed micelle formation of the phospholipid dimyristoyl phosphatidylglycerol (DMPC) and two different surfactants: the anionic surfactant sodium dodecyl sulfate (SDS) and the amphiphilic drug surfactant Sodium fusidate (SF, similar structure to that of bile salt), have been studied, and the transition from micelles to bilayers has  been determined for the different surfactants, as well as the size and structure of micelles and bilayers close to the points of transition. The self-assembly of the mixed micelles of surfactants/phospholipids have been investigated using surface tension measurements, refractive index increment and static and dynamic light scattering (SLS and DLS). The results suggest that the transition from micelles to bilayers are found to exist in the following range of bile salt/phospholipid compositions: For SF, 70-75 mol % phospholipid in the micelle was determined to be the point of transition, whilst 20-30 mol % for SDS. As the mole fractions of DMPC increased for both mixtures, the samples became turbid, which indicates the transition of micelles to bilayers. An exact value for molar ratio of transition might not be possible to determine from this study, but instead a, somewhat wider, range of values. In spite of this, a clear trend and difference between the two surfactants was observed.