Eye-concentrated distribution of dexamethasone carried by sugar-chain modified liposome in experimental autoimmune uveoretinitis mice.
Corticosteroid is generally accepted as a standard therapeutic agent for active inflammatory (and) autoimmune eye diseases. In an attempt to develop a system to deliver corticosteroid most efficiently to the target eye, a sialyl-Lewis X (sLe(x))-conjugated liposome was adopted as a candidate for a carrier of dexamethasone (Dexa) and tissue distribution of intravenous Dexa with the modified liposome as well as Dexa alone as control was studied in normal and experimental autoimmune uveoretinitis (EAU) mice. Intravenous Dexa (1 mg) was widely distributed in all the tissues (eye, brain, heart, lung, liver, kidney, spleen and intestine) examined in similar manner in both mice and Dexa concentration was lowest in the eye except the brain. The tissue concentrations of Dexa in EAU group were all significantly lower than those in the corresponding tissues in normal group. Intravenous Dexa (2 microg) in the modified liposome was almost concentrated to the eye in EAU mice, reaching 13.84 ng/mg tissue in contrast to 2.34 ng/mg tissue in Dexa (1 mg) alone administered EAU mice. In normal mice, Dexa was undetectable in any tissues examined and thus the effect of the modified liposome was not observed. The result supported the potentiality of sLe(x)-conjugated liposome for target-delivering of corticosteroid to inflamed eye.
Arakawa
Yukio
Y
Clinical Laboratory of Practical Pharmacy, Osaka University of Pharmaceutical Sciences, Takatsuki 569-1094, Japan.
Hashida
Noriyasu
N
Ohguro
Nobuyuki
N
Yamazaki
Noboru
N
Onda
Mitsuko
M
Matsumoto
Syoji
S
Ohishi
Masako
M
Yamabe
Kaoru
K
Tano
Yasuo
Y
Kurokawa
Nobuo
N
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D000818:Animals; D001327:Autoimmune Diseases / Q000378:metabolism*; D003907:Dexamethasone / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D005123:Eye / Q000378:metabolism*; D008081:Liposomes; D051379:Mice; D009844:Oligosaccharides / Q000494:pharmacology; D009928:Organ Specificity; D012173:Retinitis / Q000378:metabolism*; D000080506:Sialyl Lewis X Antigen; D014605:Uveitis / Q000378:metabolism*
D000305:Adrenal Cortex Hormones; D008081:Liposomes; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen; D003907:Dexamethasone