Specific Interaction with Hepatocytes and Acute Toxicity of New Carrier Molecule Galactosyl-Polylysine
1999
The new carrier molecules galactopyranosyl-glucuronyl-polylysines [Plys-Gal; molecular weights (MWs) of polylysine (Plys): 2,000, 10,000, and 25,000] were synthesized and their targeting characteristics to rats hepatocytes were evaluated. The maximum galactose substitution on Plys 2,000-Gal was found to be 8% of available sites. Adhesion of hepatocytes to Plys-Gal-coated dishes was inhibited by a lactosyl-polystyrene polymer (PVLA), which has been reported to be taken up via asialoglycoprotein receptors on hepatocytes. Plys 2,000-Gal had selective interaction with hepatocytes. After Plys-Gal was intravenously administered to mice (5, 10, and 20 mg/kg as Plys MW of 10,000 and 25,000), body weights were not different between mice administered Plys 10,000 or 25,000-Gal and saline as a control. It was suggested that the new carrier molecules Plys-Gals are very promising carriers for targeting drug to hepatocytes.
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