# Investigating the impact of charge and hydrophilicity on peptide-mucin interactions using a simple mucin model

## TL;DR

This study explores how the charge and hydrophilicity of peptides affect their ability to diffuse through a mucin layer, using a simple model to better understand drug transport in the gut.

## Contribution

The study introduces a simple mono-component mucin model to investigate how peptide physicochemical properties influence diffusion through intestinal mucus.

## Key findings

- Ala mutants of octreotide and lanreotide diffuse more efficiently due to reduced positive charge interactions with mucin.
- Negatively charged peptides like FITC-ADT10 diffuse faster than positively charged peptides like FITC-HAV10.
- Hydrophilicity and charge of peptides significantly influence their diffusion through mucin, with neutral and negatively charged peptides showing better performance.

## Abstract

In vitro models used to investigate drug diffusion face certain limitations and challenges because they omit for mucus interactions that could influence diffusional transport. This study developed a simple mono-component mucin model using Mucin Type II from porcine stomach to predict the effects of the physicochemical properties of peptides on their diffusion through the intestinal mucus layer. The diffusion of octreotide and lanreotide through a mucin layer was compared with their respective Ala mutants replacing Lys (i.e., octreotide A5 and lanreotide A5). Ala mutants showed higher diffusion than their respective parent peptides, implicating that the charge interaction between positively charged, Lys-containing peptide and negative charge mucin override their hydrophobic interactions, thus hindering peptide diffusion. This finding was also supported by the faster diffusion of the negatively charged FITC-ADT10 compared to the positively charged FITC-HAV10 peptide. Thus, the interaction between the peptide’s positive and the negative charge of the glycans in mucin hinders peptide diffusion.. The neutral DTPPVK has the highest hydrophilicity and diffusion compared to negatively charged DTPPD, DTPPT, and ADTC5. Although DTPPD and DTPPT have about the same hydrophilicity, DTPPD has better diffusion than DTPPT because DTPPD with −2 charges has higher negative charge repulsion against mucin compared to that of DTPPT with −1 charge. Finally, ADTC5, with the lowest hydrophilicity, has the lowest diffusion through the mucin layer. This study found that the charge and hydrophilicity of peptides influence their diffusion across the mucin layer, and these studies correlate with the previous studies utilizing different in vitro models.