title: Design of vesicles of 1,2-di-O-acyl-3-O-(beta-D-sulfoquinovosyl)-glyceride bearing two stearic acids (beta-SQDG-C18), a novel immunosuppressive drug.
abstract: The immunosuppressive effects of synthetic sulfo-glycolipids in the class of sulfoquinovosyl-diacylglycerols (SQDG), including stereoisomers, were interesting in development of a promising clinical drug. Especially, 1,2-di-O-stearoyl-3-O-(6-deoxy-6-sulfo-beta-D-glucopyranosyl)-sn-glycerol (beta-SQDG-C18) was thought to be a valuable candidate because of the preliminary observations of its high inhibitory activities in spite of low toxicities. The problem of using this material is to find an applicable way avoiding its low solubility in water. The vesicle formation of beta-SQDG-C18 is advantageous to i.v. administration in its chemico-structural character. With preparation in water, beta-SQDG-C18 was hard to form vesicles, because its hydrophilicity was strong. We examined the suitable parameter of the vesicle forming condition. It was possible to take a balance between the hydrophilicity and the hydrophobicity of the beta-SQDG-C18 molecule to be optimized to form vesicles in 150 mM PBS. In addition, we demonstrated the strong immunosuppressive activity of beta-SQDG-C18 vesicles. This is the first report of the preparation method of beta-SQDG-C18 vesicles, which should facilitate in vitro and in vivo application.
authors.affiliation: Department of Applied Biological Science, Science University of Tokyo, 2641 Yamazaki, Noda-shi, Chiba-ken 278-8510, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Mika
authors.initials: M
authors.lastname: Takenouchi
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ohta
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Ohta
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Imura
authors.forename: Masahiko
authors.initials: M
authors.lastname: Oshige
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Hiroeki
authors.initials: H
authors.lastname: Sahara
authors.forename: Hideki
authors.initials: H
authors.lastname: Sakai
authors.forename: Masahiko
authors.initials: M
authors.lastname: Abe
authors.forename: Fumio
authors.initials: F
authors.lastname: Sugawara
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sato
authors.forename: Kengo
authors.initials: K
authors.lastname: Sakaguchi
mesh_terms: D004355:Drug Stability; D005990:Glycerol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D015394:Molecular Structure; D009005:Monosaccharides / Q000138:chemical synthesis / Q000494:pharmacology*; D013229:Stearic Acids / Q000737:chemistry* / Q000494:pharmacology
chemical_list: C497947:1,2-di-O-stearoyl-3-O-(6-deoxy-6-sulfo-beta-D-glucopyranosyl)-sn-glycerol; D007166:Immunosuppressive Agents; D009005:Monosaccharides; D013229:Stearic Acids; D005990:Glycerol