High-efficacy site-directed drug delivery system using sialyl-Lewis X conjugated liposome.
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.
Department of Ophthalmology, Osaka University Graduate School of Medicine, Osaka University Medical School, E7, 2-2 Yamadaoka, Suita, Osaka 565-0871 Japan.
Noriyasu
N
Hashida
Nobuyuki
N
Ohguro
Noboru
N
Yamazaki
Yukio
Y
Arakawa
Eiji
E
Oiki
Hisashi
H
Mashimo
Nobuo
N
Kurokawa
Yasuo
Y
Tano
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001327:Autoimmune Diseases; D003907:Dexamethasone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers; D016503:Drug Delivery Systems; D019040:E-Selectin / Q000378:metabolism; D005136:Eye Proteins / Q000378:metabolism; D007983:Lewis Blood Group Antigens; D008081:Liposomes / Q000493:pharmacokinetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D053758:Nanoparticles; D009844:Oligosaccharides / Q000378:metabolism*; D019007:P-Selectin / Q000378:metabolism; D012173:Retinitis / Q000188:drug therapy / Q000378:metabolism; D000080506:Sialyl Lewis X Antigen; D014605:Uveitis / Q000188:drug therapy / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D019040:E-Selectin; D005136:Eye Proteins; D007983:Lewis Blood Group Antigens; D008081:Liposomes; D009844:Oligosaccharides; D019007:P-Selectin; D000080506:Sialyl Lewis X Antigen; D003907:Dexamethasone