Uptake by Hepatocytes and Biliary Excretion of Intravenously Administered Polystyrene Microspheres in Rats

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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.

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