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N. Hashida, N. Ohguro, Y. Tano, N. Yamasaki; In vivo Targeting of Sialyl-Lewis X Conjugated Liposome to Inflamed Site. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2650.
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E-selectin, which is expressed on activated endothelial cells, is shown to mediate endothelial cell-leukocyte adhesion by binding a sialylated carbohydrate structure, sialyl-Lewis X (SLX), found on leukocyte. The aim of this study was to evaluate the potential of SLX-conjugate liposome (sLeXL) as a site-directed delivery system to activated endothelial cells in vivo using murine experimental autoimmune uveoretinitis (EAU) model.
Four experiments were undertaken in this study. (Exp 1) Fluorescein isothiocyanate (FITC) labeled sLeXL (F-sLeXL) or its vehicle (F-L) was given intravenously as a bolus to EAU mice. Unimmunized normal mice were served as controls. Sequential tissue accumulation of both compounds was examined. (Exp2) Expression of E-selectin in EAU mice or normal mice was studied using immunohistochemistry. (Exp3) Anti-E-selectin antibody, as a blocking antibody, was given intravenously to EAU mice prior to the injection of F-sLeXL. Effect of the antibody as of inhibition of the accumulation of F-sLeXL in inflamed eye was examined. (Exp4) 2µg-dexamethasone encapsulating sLeXL (d- sLeXL) was injected intravenously as a bolus to EAU mice. Mice injected free dexamethasone solution (1mg) were served as control. Concentration of dexamethasone in several organs was measured by radioimmunoassay.
The localization of E-selectin, whose expression was not detected in normal mice, was at the same site as where FITC accumulated. Accumulation of FITC was only observed in F-sLeXL treated EAU mice. F-sLeXL accumulated at activated endothelial cells within five minutes, which was inhibited using anti-selectin antibody. The FITC color was dispersed sequentially to the entire retina. The d-sLeXL showed selective targeting to inflamed eye, where nearly two folds higher dexamethasone concentration was achieved in the eye of EAU mice compare to that with 1mg free dexamethasone.
sLeXL may be an efficient in vivo targeting delivery system to inflammatory sites.
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