En datorbaserad modell av tunntarm för utvärdering av läkemedelsformuleringar: Effekt av utspädning, lipolys och absorption på omstrukturering av solubiliserande lipidaggregat
Tidsperiod: 2014-01-01 till 2018-12-31
Projektledare: Christel Bergström
Budget: 3 943 000 SEK
A major gap to understand drug performance in the intestine is the poor knowledge of the dynamics of solubilizing lipoidal nanostructures (micelles, vesicles, oil droplets) present in the intestinal fluid. This project explores restructuring of these lipid colloids in response to intake of food or lipid-based dosage forms, enzymatic digestion and absorption. Novel experimental tools are developed to reveal the impact of these nanostructures on drug solubilization, supersaturation and likelihood of precipitation in vivo, all being important for drug absorption. The experimental results are fed into in silico models taking use of Molecular Dynamics simulations to develop a computational platform predicting drug performance in the dynamic and ever-changing intestinal milieu. The novel tools designed herein will allow dosage forms that improve performance and increase drug absorption after oral administration to, for the first time, be assessed by computational means. This will rationalize the identification of suitable formulation strategies for poorly soluble compounds, many of which not possible to study in the clinic to date. The results of the project, in particular the novel in silico tools exploring rearrangement of lipoidal nanostructures, are also highly important to related areas such as GIT disease models and food processing but also have wider applications in e.g. studies of intracellular vesicle rearrangements and transport processes in plants.