Pharmaceutical Research

, 25:1193

A Tertiary Amino-Containing Polymethacrylate Polymer Protects Mucus-Covered Intestinal Epithelial Monolayers Against Pathogenic Challenge

Authors

  • Simon Keely
    • School of Agriculture, Food Science and Veterinary Medicine and UCD Conway InstituteUniversity College Dublin
  • Lee-Anne B. Rawlinson
    • School of Agriculture, Food Science and Veterinary Medicine and UCD Conway InstituteUniversity College Dublin
  • David M. Haddleton
    • Department of ChemistryUniversity of Warwick
    • School of Agriculture, Food Science and Veterinary Medicine and UCD Conway InstituteUniversity College Dublin
Research Paper

DOI: 10.1007/s11095-007-9501-3

Cite this article as:
Keely, S., Rawlinson, L.B., Haddleton, D.M. et al. Pharm Res (2008) 25: 1193. doi:10.1007/s11095-007-9501-3

Abstract

Purpose

We examined the cytoprotective influences of the mucoadhesive polymer, poly(DMAEMA), on human mucus-producing intestinal epithelial monolayers against two bacterial exotoxins and S. typhimurium. Direct anti-bacterial effects were also assessed against S. typhimurium.

Methods

In the presence and absence of mucus, untreated or poly(DMAEMA)-exposed monolayers were challenged with S. typhimurium or supernatants containing either cholera (CTx) or C. difficile toxins. Assays included LDH, cytokine secretion, cyclic AMP (cAMP) and microscopy to visualise bacterial adherence by monolayers. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of poly(DMAEMA) against S. typhimurium were established, along with a time–kill study.

Results

CTx and C. difficile toxin induced LDH release from E12 monolayers. CTx also elevated intracellular epithelial cAMP, while S. typhimurium induced basolateral IL-8 secretion. Pre-treatment of E12 monolayers with poly(DMAEMA) reduced these effects, but only in the presence of mucus. The polymer co-localised with S. typhimurium in mucus and reduced bacteria–epithelia association. Poly(DMAEMA) was directly bactericidal against S. typhimurium at 1 mg/ml within 30 min.

Conclusions

Poly(DMAEMA) may have potential as a non-absorbed polymer therapeutic against infection. These effects were mediated by a combination of physical interaction with mucus and by direct bacterial killing.

Key words

anti-bacterial polymers bacterial resistance HT29 monolayers living radical polymerisation poly(2-(dimethylamino-ethyl) methacrylate

Abbreviations

LDH

lactate dehydrogenase

MBC

minimum bactericidal concentration

MIC

minimum inhibitory concentration

poly(DMAEMA)

poly(2-(dimethylamino-ethyl) methacrylate

Copyright information

© Springer Science+Business Media, LLC 2007