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.
Iwamoto
K
K
Department of Pharmaceutical Research, Tsukuba Research Laboratories, Eisai Company, Ltd., Ibaragi, Japan.
Kato
T
T
Kawahara
M
M
Koyama
N
N
Watanabe
S
S
Miyake
Y
Y
Sunamoto
J
J
D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002784:Cholesterol / Q000737:chemistry; D003208:Concanavalin A / Q000737:chemistry; D004337:Drug Carriers; D004655:Emulsions; D006168:Guinea Pigs; D007275:Injections, Intravenous; D008055:Lipids / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D009391:Nephelometry and Turbidimetry; D009821:Oils / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D011134:Polysaccharides / Q000737:chemistry*; D012542:Scattering, Radiation; D013499:Surface Properties; D014018:Tissue Distribution
D004337:Drug Carriers; D004655:Emulsions; D008055:Lipids; D009821:Oils; D010713:Phosphatidylcholines; D011134:Polysaccharides; D003208:Concanavalin A; D002784:Cholesterol