High-efficacy site-directed drug delivery system using sialyl-Lewis X conjugated liposome
| Autor: | Noriyasu Hashida, Nobuyuki Ohguro, Yukio Arakawa, Noboru Yamazaki, Yasuo Tano, Hisashi Mashimo, Nobuo Kurokawa, Eiji Oiki |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Anti-Inflammatory Agents
Oligosaccharides Dexamethasone Autoimmune Diseases Uveitis Mice Cellular and Molecular Neuroscience chemistry.chemical_compound Drug Delivery Systems Lewis Blood Group Antigens immune system diseases In vivo Blocking antibody medicine Animals Eye Proteins Sialyl Lewis X Antigen skin and connective tissue diseases Fluorescein isothiocyanate Drug Carriers Mice Inbred BALB C Liposome Retinitis Radioimmunoassay Molecular biology Sensory Systems Mice Inbred C57BL P-Selectin Ophthalmology chemistry Liposomes Immunology Drug delivery Nanoparticles E-Selectin Drug carrier medicine.drug |
| Zdroj: | Experimental Eye Research. 86:138-149 |
| ISSN: | 0014-4835 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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