title: Uptake by hepatocytes and biliary excretion of intravenously administered polystyrene microspheres in rats.
abstract: The in vivo uptake by hepatocytes and biliary excretion of fluorescein isothiocyanate-labeled polystyrene microsphere with a particle size of 50 nm (MS-50) after intravenous administration was studied in rats. It was confirmed by using confocal laser scanning microscopy that MS-50 was partially phagocytosed by the hepatocytes and that MS-50 taken up by the hepatocytes existed exclusively inside the cells 1 h after intravenous administration. Studies on the mechanism of the uptake of MS-50 by the hepatocytes using the liver perfusion technique revealed that a process mediated by apo-E was involved. After intravenous administration of MS-50, about 4% of dose was excreted into bile in 24 h. Pharmacokinetic evaluation of the excretion rate of MS-50 into bile showed that the process followed first-order kinetics. Qualitative evaluation of the fluorescence detected in the bile after intravenous administration of MS-50 revealed that the particles were certainly excreted into bile in an intact form. From these results, it was suggested that intravenously administered MS-50 would be partially phagocytosed by hepatocytes through a process mediated by apo-E and that MS-50 ingested by hepatocytes would be partially excreted into the bile.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ogawara
authors.forename: M
authors.initials: M
authors.lastname: Yoshida
authors.forename: K
authors.initials: K
authors.lastname: Furumoto
authors.forename: Y
authors.initials: Y
authors.lastname: Takakura
authors.forename: M
authors.initials: M
authors.lastname: Hashida
authors.forename: K
authors.initials: K
authors.lastname: Higaki
authors.forename: T
authors.initials: T
authors.lastname: Kimura
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism*; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D007275:Injections, Intravenous; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008102:Liver Circulation / Q000502:physiology; D008297:Male; D018613:Microscopy, Confocal; D008863:Microspheres; D010587:Phagocytosis; D011137:Polystyrenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D013050:Spectrometry, Fluorescence
chemical_list: D005456:Fluorescent Dyes; D011137:Polystyrenes; D016650:Fluorescein-5-isothiocyanate