alpha-Neup5Ac-(2--3)-beta-D-Galp-(1--4)-[alpha-L-Fucp-(1--3)]-D-GlcpNAc and Uveitis

The aim of this study was to evaluate the new developed sialyl-Lewis X conjugated liposome (sLe XL) 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 sLe XL (F-sLe XL) and its vehicle (F-L), sLe XL containing dexamethasone (d-sLe XL) and liposome without sLe X containing dexamethasone (d-L). First, after a bolus injection of F-sLe XL 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-sLe XL in order to investigate the effect of the antibody on inhibition of the accumulation of F-sLe XL. Third, concentration of dexamethasone in several organs after the injection of d-sLe XL (total dexamethasone 2 microg) or free dexamethasone solution (1mg) was measured by radioimmunoassay. Accumulation of FITC was only observed in F-sLe XL treated EAU mice. F-sLe XL 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-sLe XL showed selective targeting to the inflamed eye, where an approximately two-fold higher dexamethasone concentration was achieved compared with 1mg free dexamethasone. sLe XL can be a highly efficacious site-directed system in vivo. Using sLe XL as a vehicle for drug delivery, substantial pharmacologic effects with minimum side effects in inflammatory diseases should be achieved.

Topics: Animals; Anti-Inflammatory Agents; Autoimmune Diseases; Dexamethasone; Drug Carriers; Drug Delivery Systems; E-Selectin; Eye Proteins; Lewis Blood Group Antigens; Liposomes; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Nanoparticles; Oligosaccharides; P-Selectin; Retinitis; Sialyl Lewis X Antigen; Uveitis

Corticosteroid is generally accepted as a standard therapeutic agent for active inflammatory (and) autoimmune eye diseases. In an attempt to develop a system to deliver corticosteroid most efficiently to the target eye, a sialyl-Lewis X (sLe(x))-conjugated liposome was adopted as a candidate for a carrier of dexamethasone (Dexa) and tissue distribution of intravenous Dexa with the modified liposome as well as Dexa alone as control was studied in normal and experimental autoimmune uveoretinitis (EAU) mice. Intravenous Dexa (1 mg) was widely distributed in all the tissues (eye, brain, heart, lung, liver, kidney, spleen and intestine) examined in similar manner in both mice and Dexa concentration was lowest in the eye except the brain. The tissue concentrations of Dexa in EAU group were all significantly lower than those in the corresponding tissues in normal group. Intravenous Dexa (2 microg) in the modified liposome was almost concentrated to the eye in EAU mice, reaching 13.84 ng/mg tissue in contrast to 2.34 ng/mg tissue in Dexa (1 mg) alone administered EAU mice. In normal mice, Dexa was undetectable in any tissues examined and thus the effect of the modified liposome was not observed. The result supported the potentiality of sLe(x)-conjugated liposome for target-delivering of corticosteroid to inflamed eye.

Topics: Adrenal Cortex Hormones; Animals; Autoimmune Diseases; Dexamethasone; Eye; Liposomes; Mice; Oligosaccharides; Organ Specificity; Retinitis; Sialyl Lewis X Antigen; Uveitis