Dexamethasone–pDMAEMA polymeric conjugates reduce inflammatory biomarkers in human intestinal epithelial monolayers

Keely, Simon; Ryan, Sinéad M.; Haddleton, David M.; Limer, Adam; Mantovani, Giuseppe; Murphy, Evelyn P.; Colgan, Sean P.; Brayden, David J.

doi:10.1016/j.jconrel.2008.12.001

Cited by 46 publications

(29 citation statements)

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“…FITC-dextran (3 kDa) flux assays were performed in T84 intestinal epithelial cells following cytomix treatment (TNFa, IL-1b, and IFNg; 10ng/ml) in the presence of vehicle or Adora2b agonist (BAY 60-6583, 10 mM) as described 13,49 (for more details see Supplementary Materials). …”

Section: Methodsmentioning

confidence: 99%

Epithelial-specific A2B adenosine receptor signaling protects the colonic epithelial barrier during acute colitis

et al. 2015

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Central to inflammatory bowel disease (IBD) pathogenesis is loss of mucosal barrier function. Emerging evidence implicates extracellular adenosine signaling in attenuating mucosal inflammation. We hypothesized that adenosine-mediated protection from intestinal barrier dysfunction involves tissue-specific signaling through the A2B adenosine receptor (Adora2b) at the intestinal mucosal surface. To address this hypothesis, we combined pharmacologic studies and studies in mice with global or tissue-specific deletion of the Adora2b receptor. Adora2b−/− mice experienced a significantly heightened severity of colitis, associated with a more acute onset of disease and loss of intestinal epithelial barrier function. Comparison of mice with Adora2b deletion on vascular endothelial cells (Adora2bfl/flVeCadCre+) or intestinal epithelia (Adora2bfl/flVillinCre+) revealed a selective role for epithelial Adora2b signaling in attenuating colonic inflammation. In vitro studies with Adora2b knockdown in intestinal epithelial cultures or pharmacologic studies highlighted Adora2b-driven phosphorylation of vasodilator-stimulated phosphoprotein (VASP) as a specific barrier repair response. Similarly, in vivo studies in genetic mouse models or treatment studies with an Adora2b agonist (BAY 60-6583) recapitulate these findings. Taken together, our results suggest that intestinal epithelial Adora2b signaling provides protection during intestinal inflammation via enhancing mucosal barrier responses.

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Section: Methodsmentioning

confidence: 99%

Epithelial-specific A2B adenosine receptor signaling protects the colonic epithelial barrier during acute colitis

et al. 2015

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“…Steroids are commonly prescribed for acute exacerbations of both UC and CD, but prolonged use can lead to undesirable systemic sideeffects (3,4). Other therapies for IBD include aminosalicylates, antibiotics, and immunosuppressive agents.…”

Section: Introductionmentioning

confidence: 99%

Advances in oral nano-delivery systems for colon targeted drug delivery in inflammatory bowel disease: Selective targeting to diseased versus healthy tissue

Hua

Marks

Schneider

et al. 2015

Nanomedicine: Nanotechnology, Biology and Medicine

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“…However, there is currently a lack of approaches to target diseased tissue [5, 6]. Therefore, diseases of the GI tract are often treated through formulations designed for systemic administration, resulting in system-wide side effects [5, 7]. …”

Section: Introductionmentioning

confidence: 99%

Micro/nanofabricated platforms for oral drug delivery

Fox

Kim

et al. 2015

Journal of Controlled Release

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The oral route of drug administration is most preferred due to its ease of use, low cost, and high patient compliance. However, the oral uptake of many small molecule drugs and biotherapeutics is limited by various physiological barriers, and, as a result, drugs suffer from issues with low solubility, low permeability, and degradation following oral administration. The flexibility of micro- and nanofabrication techniques has been used to create drug delivery platforms designed to address these barriers to oral drug uptake. Specifically, micro/nanofabricated devices have been designed with planar, asymmetric geometries to promote device adhesion and unidirectional drug release toward epithelial tissue, thereby prolonging drug exposure and increasing drug permeation. Furthermore, surface functionalization, nanotopography, responsive drug release, motion-based responses, and permeation enhancers have been incorporated into such platforms to further enhance drug uptake. This review will outline the application of micro/nanotechnology to specifically address the physiological barriers to oral drug delivery and highlight technologies that may be incorporated into these oral drug delivery systems to further enhance drug uptake.

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Dexamethasone–pDMAEMA polymeric conjugates reduce inflammatory biomarkers in human intestinal epithelial monolayers

Cited by 46 publications

References 50 publications

Epithelial-specific A2B adenosine receptor signaling protects the colonic epithelial barrier during acute colitis

Epithelial-specific A2B adenosine receptor signaling protects the colonic epithelial barrier during acute colitis

Advances in oral nano-delivery systems for colon targeted drug delivery in inflammatory bowel disease: Selective targeting to diseased versus healthy tissue

Micro/nanofabricated platforms for oral drug delivery

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