Solid lipid nanoparticles as anti-inflammatory drug delivery system in a 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.
Department of Anatomy, Pharmacology and Forensic Medicine, University of Torino, Via P. Giuria 13, 10125 Torino, Italy. loredana.serpe@unito.it
Loredana
L
Serpe
Roberto
R
Canaparo
Marco
M
Daperno
Raffaello
R
Sostegni
Germana
G
Martinasso
Elisabetta
E
Muntoni
Laura
L
Ippolito
Nicoletta
N
Vivenza
Angelo
A
Pera
Mario
M
Eandi
Maria Rosa
MR
Gasco
Gian Paolo
GP
Zara
D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D016207:Cytokines / Q000097:blood / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000188:drug therapy*; D008055:Lipids / Q000008:administration & dosage*; D008297:Male; D053758:Nanoparticles; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013056:Spectrophotometry, Ultraviolet
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008055:Lipids