High-efficacy site-directed drug delivery system using sialyl-Lewis X conjugated liposome

The aim of this study was to evaluate the new developed sialyl-Lewis X conjugated liposome (sLeXL) as a site-directed delivery system to activated endothelial cells in vivo using a murine experimental autoimmune uveoretinitis (EAU) model. Four types of nanoparticles were prepared using this liposome: fluorescein isothiocyanate (FITC) labeled sLeXL (F-sLeXL) and its vehicle (F-L), sLeXL containing dexamethasone (d-sLeXL) and liposome without sLeX containing dexamethasone (d-L). First, after a bolus injection of F-sLeXL or F-L into EAU mice, sequential tissue accumulation of FITC was examined by confocal laser scanning microscopy. Second, anti-E-selectin antibody, as a blocking antibody, was given intravenously to EAU mice prior to the injection of F-sLeXL in order to investigate the effect of the antibody on inhibition of the accumulation of F-sLeXL. Third, concentration of dexamethasone in several organs after the injection of d-sLeXL (total dexamethasone 2 μg) or free dexamethasone solution (1 mg) was measured by radioimmunoassay. Accumulation of FITC was only observed in F-sLeXL treated EAU mice. F-sLeXL accumulated on the activated endothelial cells within 5 min; accumulation then was inhibited using anti-E-selectin antibody. The FITC color was dispersed sequentially to the entire retina. d-sLeXL showed selective targeting to the inflamed eye, where an approximately two-fold higher dexamethasone concentration was achieved compared with 1 mg free dexamethasone. sLeXL can be a highly efficacious site-directed system in vivo. Using sLeXL as a vehicle for drug delivery, substantial pharmacologic effects with minimum side effects in inflammatory diseases should be achieved.