Solid lipid nanoparticles as anti-inflammatory drug delivery system in a human inflammatory bowel disease whole-blood model

• Published in: European journal of pharmaceutical sciences Vol. 39; no. 5; pp. 428 - 436
• Main Authors: Serpe, Loredana, Canaparo, Roberto, Daperno, Marco, Sostegni, Raffaello, Martinasso, Germana, Muntoni, Elisabetta, Ippolito, Laura, Vivenza, Nicoletta, Pera, Angelo, Eandi, Mario, Gasco, Maria Rosa, Zara, Gian Paolo
• Format: Journal Article
• Language: English
• Published: Kindlington Elsevier B.V 18.03.2010; Elsevier
• Subjects: Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - therapeutic use; Biological and medical sciences; Butyrate; Chromatography, High Pressure Liquid; Cytokines; Cytokines - blood; Cytokines - genetics; Dexamethasone; Enzyme-Linked Immunosorbent Assay; Female; General pharmacology; Humans; Inflammatory bowel diseases; Inflammatory Bowel Diseases - blood; Inflammatory Bowel Diseases - drug therapy; Lipids - administration & dosage; Male; Medical sciences; Nanoparticles; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Reverse Transcriptase Polymerase Chain Reaction; Solid lipid nanoparticles; Spectrophotometry, Ultraviolet; Inflammatory bowel diseases; Dexamethasone; Cytokines; Solid lipid nanoparticles; Butyrate; Human; Corticosteroid; Biological fluid; Pharmaceutical technology; Steroid hormone; Antiinflammatory agent; Cytokine; Drug carrier; Blood; Inflammatory disease; Crohn disease; Digestive diseases; Intestinal disease; Ulcerative colitis
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2010.01.013

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-1β, TNF-α, IFN-γ and IL-10 secretion in inflammatory bowel diseases patients’ PBMC culture supernatants. There was a significant decrease in IL-1β ( p < 0.01) and TNF-α ( 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 μM), at 24 h exposure. There was a significant decrease in IL-1β ( p < 0.01), TNF-α ( 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 24 h exposure. No IFN-γ 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.