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

Benyamin Naranjani; Patrick D Sinko; Christel A S Bergström; Adolf Gogoll; Shakhawath Hossain; Per Larsson

doi:10.1016/j.ijbiomac.2023.124388

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

Int J Biol Macromol. 2023 Jun 15:240:124388. doi: 10.1016/j.ijbiomac.2023.124388. Epub 2023 Apr 12.

Authors

Benyamin Naranjani¹, Patrick D Sinko², Christel A S Bergström³, Adolf Gogoll⁴, Shakhawath Hossain², Per Larsson⁵

Affiliations

¹ Department of Pharmacy, Uppsala Biomedical Center, Uppsala University, 751 23 Uppsala, Sweden; Swedish Drug Delivery Center (SweDeliver), Uppsala University, 751 23 Uppsala, Sweden. Electronic address: benyamin.naranjani@farmaci.uu.se.
² Department of Pharmacy, Uppsala Biomedical Center, Uppsala University, 751 23 Uppsala, Sweden.
³ Department of Pharmacy, Uppsala Biomedical Center, Uppsala University, 751 23 Uppsala, Sweden; Swedish Drug Delivery Center (SweDeliver), Uppsala University, 751 23 Uppsala, Sweden.
⁴ Department of Chemistry, Uppsala Biomedical Center, Uppsala University, 751 23 Uppsala, Sweden.
⁵ Department of Pharmacy, Uppsala Biomedical Center, Uppsala University, 751 23 Uppsala, Sweden; Swedish Drug Delivery Center (SweDeliver), Uppsala University, 751 23 Uppsala, Sweden. Electronic address: per.r.larsson@uu.se.

PMID: 37059282
DOI: 10.1016/j.ijbiomac.2023.124388

Abstract

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 (C₁₀) are used to represent the general class of MM and PE molecules. Nuclear magnetic resonance spectroscopy was used to obtain the diffusivity of C₁₀, and coarse-grain molecular dynamics simulations were carried out to estimate the concentration-dependent diffusivity of C₁₀. 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^-1. 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.

Keywords: Bioavailability; Computational modeling; Molecular diffusivity; Oral delivery; Peristaltic motility; Permeation enhancement.

MeSH terms

Biological Transport
Intestine, Small*
Peristalsis* / physiology