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 β ‐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.British Journal of Pharmacology (2006) 148 , 648–656. doi: 10.1038/sj.bjp.0706761