Keely, Simon, Rawlinson, Lee-Anne B., Haddleton, David M. and Brayden, David J.. (2008) A tertiary amino-containing polymethacrylate polymer protects mucus-covered intestinal epithelial monolayers against pathogenic challenge. Pharmaceutical Research, Vol.25 (No.5). pp. 1193-1201. ISSN 0724-8741

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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.

Item Type:	Journal Article
Subjects:	Q Science > QD Chemistry Q Science > QR Microbiology > QR180 Immunology R Medicine > RS Pharmacy and materia medica
Divisions:	Faculty of Science > Chemistry
Library of Congress Subject Headings (LCSH):	Polymers, Drug resistance in microorganisms, Pathogenic microorganisms, Polymerization, Antimicrobial polymers
Journal or Publication Title:	Pharmaceutical Research
Publisher:	Springer New York LLC
ISSN:	0724-8741
Date:	May 2008
Volume:	Vol.25
Number:	No.5
Number of Pages:	9
Page Range:	pp. 1193-1201
Identification Number:	10.1007/s11095-007-9501-3
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
URI:	http://wrap.warwick.ac.uk/id/eprint/30257

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