Design of vesicles of 1,2-di-O-acyl-3-O-(β-D-sulfoquinovosyl)-glyceride bearing two stearic acids (β-SQDG-C18), a novel immunosuppressive drug

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-C-18) 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-C-18 is advantageous to i.v. administration in its chemico-structural character. With preparation in water, beta-SQDG-C-18 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-C-18 molecule to be optimized to form vesicles in 150 mM PBS. In addition, we demonstrated the strong immunosuppressive activity of beta-SQDG-C-18 vesicles. This is the first report of the preparation method of beta-SQDG-C-18 vesicles, which should facilitate in vitro and in vivo application. (C) 2004 Elsevier Inc. All rights reserved.