Polysaccharide-coated oil droplets in oil-in-water emulsions as targetable carriers for lipophilic drugs.

Surface of oil droplets in an oil-in-water (o/w) emulsion were coated with naturally occurring polysaccharides (such as mannan, amylopectin, and pullulan) which were, in part, bearing a cholesterol moiety. The mean size of the colloidal droplets was not altered much, even by coating with the polysaccharide derivatives, while the surface charge of the droplet decreased upon coating. Mannan and amylopectin derivative-coated droplets aggregated upon addition of Concanavalin A. These observations suggest that the terminal sugar moiety of the specific polysaccharides on the surface of colloidal droplets can be recognized by lectin. After intravenous injection of the emulsions into guinea pigs, kinetics of the blood clearance and the tissue distribution of the polysaccharide-coated oil droplets, which contain [14C]coenzyme Q10 as the marker, were investigated. In the initial rapid phase of blood clearance of the radioactivity, the polysaccharide-coated droplets were cleared from the blood stream slower than the uncoated ones. The lung uptake of the mannan derivative-coated droplet emulsion at 30 min after intravenous injection was approximately 15 times higher than that of the conventional emulsion without the polysaccharide coat.

[1]  Toshinori Sato,et al.  Physicochemical Stabilization of Lipid Microspheres by Coating with Polysaccharide Derivatives , 1989 .

[2]  P. Artursson,et al.  Biopharmaceutics of Microparticulate Drug Carriers , 1987, Annals of the New York Academy of Sciences.

[3]  S. Davis,et al.  Targeting of colloidal particles to the bone marrow. , 1987, Life sciences.

[4]  K. Hoshi,et al.  Marked enhancement in antithrombotic activity of isocarbacyclin following its incorporation into lipid microspheres. , 1987, Prostaglandins.

[5]  F. Ishii,et al.  [Evaluation of the emulsifying activity of saturated egg phosphatide hydrogenation for the O/W type emulsion]. , 1985, Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan.

[6]  K. Katayama,et al.  Increased lung uptake of liposomes coated with polysaccharides. , 1984, Biochimica et biophysica acta.

[7]  Y. Mizushima,et al.  Tissue distribution and anti-inflammatory activity of corticosteroids incorporated in lipid emulsion. , 1982, Annals of the rheumatic diseases.

[8]  Mark J. Miller,et al.  Evidence for receptor-mediated binding of glycoproteins, glycoconjugates, and lysosomal glycosidases by alveolar macrophages. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[9]  N. Sharon,et al.  Lectins: cell-agglutinating and sugar-specific proteins. , 1972, Science.

[10]  J. Hartwig,et al.  Quantitative studies of phagocytosis by polymorphonuclear leukocytes: use of emulsions to measure the initial rate of phagocytosis. , 1972, The Journal of clinical investigation.

[11]  L. Utracki,et al.  Current topics in polymer science , 1987 .

[12]  S. Davis,et al.  Poly(butyl 2-cyanoacrylate) nanoparticles with differing surface charges , 1986 .

[13]  Y. Mizushima.  Lipid microspheres as novel drug carriers. , 1985, Drugs under experimental and clinical research.

[14]  S. Davis,et al.  The influence of emulsifying agents on the phagocytosis of lipid emulsions by macrophages , 1985 .