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.
Hashida
Noriyasu
N
Department of Ophthalmology, Osaka University Graduate School of Medicine, Osaka University Medical School, E7, 2-2 Yamadaoka, Suita, Osaka 565-0871 Japan.
Ohguro
Nobuyuki
N
Yamazaki
Noboru
N
Arakawa
Yukio
Y
Oiki
Eiji
E
Mashimo
Hisashi
H
Kurokawa
Nobuo
N
Tano
Yasuo
Y
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