Stability of Carbohydrate-Modified Vesicles in vivo: Comparative Effects of Ceramide and Cholesterol Glycoconjugates

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 79; no. 18; pp. 5490 - 5493
• Main Authors: Wu, Po-Shun, Wu, Hsiu-Mei, Tin, George W., Schuh, Joseph R., Croasmun, William R., Baldeschwieler, John D., Shen, T. Y., Ponpipom, M. M.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 01.09.1982; National Acad Sciences
• Subjects: Administration, Oral; Aggregation; Animals; Biochemistry; Ceramides; Cerebrosides; Cerebrosides - metabolism; Cholesterol - analogs & derivatives; Cholesterol - metabolism; Cholesterols; Drug Stability; Galactosylceramides - metabolism; Injections, Intraperitoneal; Intravesical administration; Kinetics; Lipids; Liposomes - administration & dosage; Mice; Microscopy, Electron; Oral administration; Phosphatidylcholines - metabolism; Stomach; Temperature; Tissue Distribution
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.79.18.5490

The stability and tissue distribution of lipid vesicles modified at the surface by the incorporation of either a galactosyl ceramide (GalCer) or a galactosyl cholesterol (GalChol) glycoconjugate have been studied in mice by measuring the release of vesicle-entrapped111In. Although the tissue distributions of both vesicle types were similar, the GalCer-containing vesicles were markedly less stable than those prepared with GalChol, whether administered orally or by intraperitoneal injection. Physical characterization of the vesicles in vitro suggests that the increased disruption rate for GalCer vesicles in vivo is related to structural instabilities induced by the cerebroside, which can then result in either an increased rate of vesicle uptake by tissues or a greater susceptibility to lysis. These studies demonstrate the importance of the nonpolar anchoring groups in determining the fate of surface-modified vesicles in vivo.