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DNBS/TNBS Colitis Models: Providing Insights Into Inflammatory Bowel Disease and Effects of Dietary Fat
Published on: February 27, 2014
Solid lipid nanoparticles as anti-inflammatory drug delivery system in a human inflammatory bowel disease whole-blood
Loredana Serpe1, Roberto Canaparo, Marco Daperno
1Department of Anatomy, Pharmacology and Forensic Medicine, University of Torino, Via P. Giuria 13, 10125 Torino, Italy. loredana.serpe@unito.it
Standard treatment for inflammatory bowel diseases (IBD) necessitates frequent intake of anti-inflammatory and/or immunosuppressive drugs, leading to significant adverse events. To evaluate the role solid lipid nanoparticles (SLN) play as drug delivery system in enhancing anti-inflammatory activity for drugs such as dexamethasone and butyrate in a human inflammatory bowel diseases whole-blood model. ELISA assay and the peripheral blood mononuclear cell (PBMC) cytokine mRNA expression levels were evaluated by quantitative SYBR Green real-time RT-PCR to determine the IL-1beta, TNF-alpha, IFN-gamma and IL-10 secretion in inflammatory bowel diseases patients' PBMC culture supernatants. There was a significant decrease in IL-1beta (p<0.01) and TNF-alpha (p<0.001) secretion, whilst IL-10 (p<0.05) secretion significantly increased after cholesteryl butyrate administration, compared to that of butyrate alone at the highest concentration tested (100 microM), at 24h exposure. There was a significant decrease in IL-1beta (p<0.01), TNF-alpha (p<0.001) and IL-10 (p<0.001) secretion after dexamethasone loaded SLN administration, compared to dexamethasone alone at the highest concentration tested (250 nM) at 24h exposure. No IFN-gamma was detected under any conditions and no cytotoxic effects observed even at the highest concentration tested. The incorporation of butyrate and dexamethasone into SLN has a significant positive anti-inflammatory effect in the human inflammatory bowel disease whole-blood model.
Standard treatment for inflammatory bowel diseases (IBD) necessitates frequent intake of anti-inflammatory and/or immunosuppressive drugs, leading to significant adverse events. To evaluate the role solid lipid nanoparticles (SLN) play as drug delivery system in enhancing anti-inflammatory activity for drugs such as dexamethasone and butyrate in a human inflammatory bowel diseases whole-blood model. ELISA assay and the peripheral blood mononuclear cell (PBMC) cytokine mRNA expression levels were evaluated by quantitative SYBR Green real-time RT-PCR to determine the IL-1beta, TNF-alpha, IFN-gamma and IL-10 secretion in inflammatory bowel diseases patients' PBMC culture supernatants. There was a significant decrease in IL-1beta (p<0.01) and TNF-alpha (p<0.001) secretion, whilst IL-10 (p<0.05) secretion significantly increased after cholesteryl butyrate administration, compared to that of butyrate alone at the highest concentration tested (100 microM), at 24h exposure. There was a significant decrease in IL-1beta (p<0.01), TNF-alpha (p<0.001) and IL-10 (p<0.001) secretion after dexamethasone loaded SLN administration, compared to dexamethasone alone at the highest concentration tested (250 nM) at 24h exposure. No IFN-gamma was detected under any conditions and no cytotoxic effects observed even at the highest concentration tested. The incorporation of butyrate and dexamethasone into SLN has a significant positive anti-inflammatory effect in the human inflammatory bowel disease whole-blood model.
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