Application of sialyl-Lewis X conjugated liposome to the murine experimental autoimmune uveoretinitis

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(Purpose)The purposes of this study are to investigate the molecular function of Sialyl-Lewis X conjugated liposome (SLX (+) liposome) in murine experimental autoimmune uveoretinitis (EAU) and to examine whether it may become the active targeting drug delivery system (ATDDS) aiming at E-selectin as a molecule the target.(Methods)For organ distribution analysis of liposome, three experiments were performed. (Exp.1) Fluorescein isothiocyanate (FITC) labeled SLX (+) liposome was administered to EAU mice and accumulation of FITC fluorescence to the choroid and retina was observed. Normal mice were used as controls. Same experiments using the liposome which does not conjugate SLX (SLX (-) liposome) were performed. (Exp.2) Immunostaining of E-selectin in the eye of EAU mice were performed. We examined whether it would be the same as the accumulation part of the FITC labeled SLX (+) liposome. (Exp.3) After administration of anti E-selectin neutralization antibody to EAU mice, FITC labeled SLX (+) liposome was injected to EAU mice. Binding inhibition of SLX (+) liposome to E-selectin was observed.(Results)Accumulation of FITC was observed only when EAU mice were administered with SLX (+) liposome. Accumulation of FITC was in agreement with E-selectin expression. Binding of SLX (+) liposome to E-selectin was inhibited by neutralization antibody to E-selectin.(Discussion)SLX, an oligosaccharide on the surface of a leukocyte, is known to combine with E-selectin on the vascular endothelial cells. Our results suggest that SLX (+) liposome operates similarly to leukocytes at the site of inflammation. This SLX conjugated liposome that targets at E-selectin might serve as ATDDS.