Nanostructure formation during lipid digestion

An increasing number of new drug compounds are poorly water-soluble in nature, leading to limited solubility and absorption in the gastrointestinal tract, and hence low and variable bioavailability. Lipid-based formulations are increasingly viewed as an avenue to enhance the delivery of such drug molecules. During the digestion of formulation components, the lipolysis products disperse in the gastrointestinal environment and self-assemble into colloidal phases, enabling drug solubilisation. Traditionally, the focus of research in these formulations has been on the compositional aspects, due to a lack of methods to study structure formation in real-time. To address this current shortcoming, the research undertaken in this thesis examines structure formation in the gastrointestinal tract during lipid digestion. Two approaches have been examined; equilibrium and dynamic studies. In equilibrium studies, bile salt/phospholipid mixed micelles upon incorporation of monoglycerides and fatty acids were studied by scattering and microscopy techniques to determine the influence of pH, temperature and lipid chain length on self-assembly behaviour. An in vitro lipolysis model coupled to synchrotron small angle X-ray scattering was employed for structural studies in real-time, where structure formation was linked to composition using pH stat titration, cryogenic-transmission electron microscopy and high performance liquid chromatography. In addition, the possibility of using an immobilised lipase to address drawbacks in the use of porcine pancreatic lipase for in vitro lipolysis experiments, particularly in terms of scattering measurements was investigated. The studies described in this thesis have provided new approaches and insights into structure formation during lipid digestion and further understanding for the rational design of lipid-based drug formulations.