The Library
Dexamethasone-pDMAEMA polymeric conjugates reduce inflammatory biomarkers in human intestinal epithelial monolayers
Tools
Keely, Simon, Ryan, Sinead M., Haddleton, David M., Limer, Adam, Mantovani, Giuseppe, Murphy, Evelyn P., Colgan, Sean P. and Brayden, David J. (2009) Dexamethasone-pDMAEMA polymeric conjugates reduce inflammatory biomarkers in human intestinal epithelial monolayers. Journal of Controlled Release, Vol.135 (No.1). pp. 35-43. doi:10.1016/j.jconrel.2008.12.001 ISSN 01683659.
Research output not available from this repository.
Request-a-Copy directly from author or use local Library Get it For Me service.
Official URL: http://dx.doi.org/10.1016/j.jconrel.2008.12.001
Abstract
The mucoadhesive polymer, poly(dimethylamino)ethyl methacrylate, (pDMAEMA), was synthesised by living radical polymerisation and subsequently conjugated by quaternisation reaction to a functionalised anti-inflammatory corticosteroid dexamethasone, to separately yield two conjugates with either 9:1 or 18:1 molar ratios of dexamethasone: polymer respectively. The hypothesis was to test whether the active agent maintained in vitro bioactivity when exposed to the apical side of human intestinal epithelial monolayers, Caco-2 and mucos-covered HT29-MTX-E12 (E12). HPLC analysis indicated high conjugate purity. Similar to pDMAEMA, fluorescently-labelled dexamethasone-pDMAEMA conjugates were bioadhesive to Caco-2 and mucoadhesive to E12. Apical addition of conjugates suppressed mRNA expression of the inflammatory markers, NURR1 and ICAM-1 in E12 following stimulation by PGE(2) and TNF-alpha, respectively. Conjugates also suppressed TNF-alpha stimulated cytokine secretion to the basolateral side of Caco-2 monolayers. Measurement of dexamethasone permeability from conjugates across monolayers suggested that conjugation reduced permeability compared to free dexamethasone. LDH assay indicated that conjugates were not cytotoxic to monolayers. Anti-inflammatory agents can therefore be successfully conjugated to polymers and they retain adhesion and bioactivity and have potential to be formulated for topical administration. (C) 2008 Elsevier B.V. All rights reserved.
Item Type: | Journal Article | ||||
---|---|---|---|---|---|
Subjects: | Q Science > QD Chemistry R Medicine > RS Pharmacy and materia medica |
||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry | ||||
Journal or Publication Title: | Journal of Controlled Release | ||||
Publisher: | Elsevier BV | ||||
ISSN: | 01683659 | ||||
Official Date: | 2 April 2009 | ||||
Dates: |
|
||||
Volume: | Vol.135 | ||||
Number: | No.1 | ||||
Number of Pages: | 9 | ||||
Page Range: | pp. 35-43 | ||||
DOI: | 10.1016/j.jconrel.2008.12.001 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Restricted or Subscription Access | ||||
Funder: | Science Foundation Ireland Investigator grant | ||||
Grant number: | 04 IN3 B575 |
Data sourced from Thomson Reuters' Web of Knowledge
Request changes or add full text files to a record
Repository staff actions (login required)
View Item |