Numerical simulation of peristalsis to study co-localization and intestinal distribution of a macromolecular drug and permeation enhancer.

In this work, simulations of intestinal peristalsis are performed to investigate the intraluminal transport of macromolecules (MMs) and permeation enhancers (PEs). Properties of insulin and sodium caprate (C) are used to represent the general class of MM and PE molecules. Nuclear magnetic resonance spectroscopy was used to obtain the diffusivity of C, and coarse-grain molecular dynamics simulations were carried out to estimate the concentration-dependent diffusivity of C. A segment of the small intestine with the length of 29.75 cm was modeled. Peristaltic speed, pocket size, release location, and occlusion ratio of the peristaltic wave were varied to study the effect on drug transport. It was observed that the maximum concentration at the epithelial surface for the PE and the MM increased by 397 % and 380 %, respectively, when the peristaltic wave speed was decreased from 1.5 to 0.5 cm s. At this wave speed, physiologically relevant concentrations of PE were found at the epithelial surface. However, when the occlusion ratio is increased from 0.3 to 0.7, the concentration approaches zero. These results suggest that a slower-moving and more contracted peristaltic wave leads to higher efficiency in transporting mass to the epithelial wall during the peristalsis phases of the migrating motor complex.