TY  - JOUR
  - McCarthy, J,O'Neill, MJ,Bourre, L,Walsh, D,Quinlan, A,Hurley, G,Ogier, J,Shanahan, F,Melgar, S,Darcy, R,O'Driscoll, CM
  - 2013
  - May
  - Journal of controlled release : official journal of the Controlled Release Society
  - Gene silencing of TNF-alpha in a murine model of acute colitis using a modified cyclodextrin delivery system
  - Validated
  - Altmetric: 1 ()
  - Cyclodextrin siRNA delivery TNF-alpha Inflammatory bowel disease Murine model of acute-colitis Intrarectal administration INFLAMMATORY-BOWEL-DISEASE SIRNA DELIVERY ULCERATIVE-COLITIS AMPHIPHILIC CYCLODEXTRINS MICE TRANSFECTION EXPRESSION INDUCTION THERAPIES VECTORS
  - 168
  - 28
  - 34
  - Inflammatory bowel disease (IBD) is a chronic relapsing inflammation of the gastrointestinal tract. The cytokine TNF-alpha (TNF-alpha) plays a pivotal role in mediating this inflammatory response. RNA interference (RNAi) holds great promise for the specific and selective silencing of aberrantly expressed genes, such as TNF-alpha in IBD. The aim of this study was to investigate the efficacy of an amphiphilic cationic cyclodextrin (CD) vector for effective TNF-alpha siRNA delivery to macrophage cells and to mice with induced acute-colitis. The stability of CD. siRNA was examined by gel electrophoresis in biorelevant media reflecting colonic fluids. RAW264.7 cells were transfected with CD. TNF-alpha siRNA, stimulated with lipopolysaccharide (LPS) and TNF-alpha and IL-6 responses were measured by PCR and ELISA. Female C57BL/6 mice were exposed to dextran sodium sulphate (DSS) and treated by intrarectal administration with either CD. siRNA TNF-alpha or a control solution. In vitro, siRNA in CD nanocomplexes remained intact and stable in both fed and fasted simulated colonic fluids. RAW264.7 cells transfected with CD. TNF-alpha siRNA and stimulated with LPS displayed a significant reduction in both gene and protein levels of TNF-alpha and IL-6. CD. TNF-alpha siRNA-treated mice revealed a mild amelioration in clinical signs of colitis, but significant reductions in total colon weight and colonic mRNA expression of TNF-a and IL-6 compared to DSS-control mice were detected. This data indicates the clinical potential of a local CD-based TNF-alpha siRNA delivery system for the treatment of IBD. (C) 2013 Elsevier B.V. All rights reserved.
  - 10.1016/j.jconrel.2013.03.004
DA  - 2013/05
ER  - 

@article{V243938907,
   = {McCarthy,  J and O'Neill,  MJ and Bourre,  L and Walsh,  D and Quinlan,  A and Hurley,  G and Ogier,  J and Shanahan,  F and Melgar,  S and Darcy,  R and O'Driscoll,  CM },
   = {2013},
   = {May},
   = {Journal of controlled release : official journal of the Controlled Release Society},
   = {Gene silencing of TNF-alpha in a murine model of acute colitis using a modified cyclodextrin delivery system},
   = {Validated},
   = {Altmetric: 1 ()},
   = {Cyclodextrin siRNA delivery TNF-alpha Inflammatory bowel disease Murine model of acute-colitis Intrarectal administration INFLAMMATORY-BOWEL-DISEASE SIRNA DELIVERY ULCERATIVE-COLITIS AMPHIPHILIC CYCLODEXTRINS MICE TRANSFECTION EXPRESSION INDUCTION THERAPIES VECTORS},
   = {168},
  pages = {28--34},
   = {{Inflammatory bowel disease (IBD) is a chronic relapsing inflammation of the gastrointestinal tract. The cytokine TNF-alpha (TNF-alpha) plays a pivotal role in mediating this inflammatory response. RNA interference (RNAi) holds great promise for the specific and selective silencing of aberrantly expressed genes, such as TNF-alpha in IBD. The aim of this study was to investigate the efficacy of an amphiphilic cationic cyclodextrin (CD) vector for effective TNF-alpha siRNA delivery to macrophage cells and to mice with induced acute-colitis. The stability of CD. siRNA was examined by gel electrophoresis in biorelevant media reflecting colonic fluids. RAW264.7 cells were transfected with CD. TNF-alpha siRNA, stimulated with lipopolysaccharide (LPS) and TNF-alpha and IL-6 responses were measured by PCR and ELISA. Female C57BL/6 mice were exposed to dextran sodium sulphate (DSS) and treated by intrarectal administration with either CD. siRNA TNF-alpha or a control solution. In vitro, siRNA in CD nanocomplexes remained intact and stable in both fed and fasted simulated colonic fluids. RAW264.7 cells transfected with CD. TNF-alpha siRNA and stimulated with LPS displayed a significant reduction in both gene and protein levels of TNF-alpha and IL-6. CD. TNF-alpha siRNA-treated mice revealed a mild amelioration in clinical signs of colitis, but significant reductions in total colon weight and colonic mRNA expression of TNF-a and IL-6 compared to DSS-control mice were detected. This data indicates the clinical potential of a local CD-based TNF-alpha siRNA delivery system for the treatment of IBD. (C) 2013 Elsevier B.V. All rights reserved.}},
   = {10.1016/j.jconrel.2013.03.004},
  source = {IRIS}
}