posted on 2020-09-08, 14:49authored byAlbin Parrow, Per Larsson, Patrick Augustijns, Christel A. S. Bergström
Efficient delivery
of oral drugs is dependent on their solubility
in human intestinal fluid, a complex and dynamic fluid that contains
colloidal structures composed of small molecules. These structures
solubilize poorly water-soluble compounds, increasing their apparent
solubility, and possibly their bioavailability. In this study, we
conducted coarse-grained molecular dynamics simulations with data
from duodenal fluid samples previously acquired from five healthy
volunteers. In these simulations, we observed the self-assembly of
mixed micelles of bile salts, phospholipids, and free fatty acids.
The micelles were ellipsoids with a size range of 4–7 nm. Next,
we investigated micelle affinities of three model drugs. The affinities
in our simulation showed the same trend as literature values for the
solubility enhancement of drugs in human intestinal fluids. This type
of simulations is useful for studies of events and interactions taking
place in the small intestinal fluid.