TY  - JOUR
  - McCarthy, J.,O'Neill, M. J.,Bourre, L.,Walsh, D.,Quinlan, A.,Hurley, G.,Ogier, J.,Shanahan, F.,Melgar, S.,Darcy, R.,O'Driscoll, C. M.
  - 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
  - ()
  - 168
  - 1
  - 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.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.
  - 0168-36590168-3659
  - ://WOS:000319498900004://WOS:000319498900004
DA  - 2013/05
ER  - 

@article{V235378853,
   = {McCarthy,  J. and O'Neill,  M. J. 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,  C. M. },
   = {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},
   = {()},
   = {168},
   = {1},
  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.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.}},
  issn = {0168-36590168-3659},
   = {://WOS:000319498900004://WOS:000319498900004},
  source = {IRIS}
}