May 2007
Volume 48, Issue 13
ARVO Annual Meeting Abstract  |   May 2007
In vivo Targeting of Sialyl-Lewis X Conjugated Liposome to Inflamed Site
Author Affiliations & Notes
  • N. Hashida
    Dept of Ophthalmology, Osaka Univ Medical School, Suita, Japan
  • N. Ohguro
    Dept of Ophthalmology, Osaka Univ Medical School, Suita, Japan
  • Y. Tano
    Dept of Ophthalmology, Osaka Univ Medical School, Suita, Japan
  • N. Yamasaki
    Advanced Industrial Science and Technology, Tsukuba, Japan
  • Footnotes
    Commercial Relationships N. Hashida, None; N. Ohguro, None; Y. Tano, None; N. Yamasaki, None.
  • Footnotes
    Support None.
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 2650. doi:
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    • Get Citation

      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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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose:: 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.

Methods:: 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.

Results:: 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.

Conclusions:: sLeXL may be an efficient in vivo targeting delivery system to inflammatory sites.

Keywords: uveitis-clinical/animal model • inflammation • drug toxicity/drug effects 

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