Cholesteryl butyrate solid lipid nanoparticles inhibit adhesion of human neutrophils to endothelial cells.
1. Adhesion of polymorphonuclear cells (PMNs) to vascular endothelial cells (EC) is a critical step in recruitment and infiltration of leukocytes into tissues during inflammation. High doses of butyric acid have been shown to ameliorate inflammation in inflammatory bowel diseases (IBD). Cholesteryl-butyrate solid lipid nanoparticles (chol-but SLN) as prodrug are a possible delivery system for butyric acid. 2. Sodium butyrate or chol-but SLN were coincubated with human PMNs and human umbilical vein EC (HUVEC); adhesion was quantified by computerized microimaging fluorescence analysis. Both chol-but SLN and sodium butyrate displayed antiadhesive effects on FMLP- and IL-1beta-stimulated cells in a concentration-response curve (10(-8)-10(-5) M), but chol-but SLN were in all cases more active. Moreover, chol-but SLN inhibited FMLP-induced adhesion of PMNs to FCS-coated plastic wells, thus showing a direct effect on PMNs, while sodium butyrate had little effect. Confocal microscopy showed that fluorescent SLN entered PMNs and HUVEC after 10 min incubation. Chol-but SLN acted either on activated PMN or HUVEC. 3. Chol-but SLN inhibited O2-* production and myeloperoxidase release by PMNs evoked by FMLP, in a dose-dependent, but not time-dependent, manner and were more active than sodium butyrate. 4. In conclusion, in all tests chol-but SLN were more active than sodium butyrate. Thus, chol-but SLN might be a valid alternative to sodium butyrate in the anti-inflammatory therapy of ulcerative colitis, avoiding complications related to the administration of sodium butyrate.
Dianzani
Chiara
C
Department of Anatomy, Pharmacology and Forensic Medicine, University of Turin, Torino 10125, Italy. chiara.dianzani@unito.it
Cavalli
Roberta
R
Zara
Gian Paolo
GP
Gallicchio
Margherita
M
Lombardi
Grazia
G
Gasco
Maria Rosa
MR
Panzanelli
Patrizia
P
Fantozzi
Roberto
R
D002087:Butyrates / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects*; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D008055:Lipids / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D053758:Nanoparticles / Q000737:chemistry; D009504:Neutrophils / Q000187:drug effects*; D009195:Peroxidase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D002087:Butyrates; D002788:Cholesterol Esters; D053583:Interleukin-1beta; D008055:Lipids; D013481:Superoxides; C053743:cholesteryl octanoate; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009195:Peroxidase