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A tertiary amino-containing polymethacrylate polymer protects mucus-covered intestinal epithelial monolayers against pathogenic challenge.

AbstractPURPOSE:
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.
AuthorsSimon Keely, Lee-Anne B Rawlinson, David M Haddleton, David J Brayden
JournalPharmaceutical research (Pharm Res) Vol. 25 Issue 5 Pg. 1193-201 (May 2008) ISSN: 0724-8741 [Print] United States
PMID18046631 (Publication Type: Journal Article)
Chemical References
  • Anti-Bacterial Agents
  • Fluorescent Dyes
  • Interleukin-8
  • Methacrylates
  • Nylons
  • Protective Agents
  • poly(2-(diethylamino)ethyl methacrylate)
  • Cholera Toxin
  • Cyclic AMP
  • L-Lactate Dehydrogenase
Topics
  • Anti-Bacterial Agents (chemistry, pharmacology)
  • Bacterial Adhesion (drug effects)
  • Cholera Toxin (antagonists & inhibitors)
  • Cyclic AMP (metabolism)
  • Fluorescent Dyes
  • HT29 Cells
  • Humans
  • Interleukin-8 (metabolism)
  • Intestinal Mucosa (drug effects, microbiology)
  • L-Lactate Dehydrogenase (metabolism)
  • Methacrylates (chemical synthesis, chemistry, pharmacology)
  • Microbial Sensitivity Tests
  • Mucus (drug effects, physiology)
  • Nylons (chemical synthesis, chemistry, pharmacology)
  • Protective Agents (chemistry, pharmacology)
  • Salmonella Infections (prevention & control)
  • Salmonella typhimurium (drug effects, growth & development)

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