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-1 beta-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 O-2(-). 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.