Lactose-carrying polystyrene as a drug carrier: investigation of body distributions to parenchymal liver cells using 125I-labelled lactose-carrying polystyrene

• Published in: Journal of controlled release Vol. 28; no. 1; pp. 223 - 233
• Main Authors: Mitsuaki, Goto, Hirohumi, Yura, Chia-Wun, Chang, Akira, Kobayashi, Tatsuki, Shinoda, Atsushi, Maeda, Seiki, Kojima, Kazukiyo, Kobayashi, Toshihiro, Akaike
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Amsterdam Elsevier B.V 1994; Elsevier
• Subjects: Asialoglycoprotein receptor; Biological and medical sciences; Drug delivery system; General pharmacology; Hepatocyte; Medical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; PVLA; Saccharide recognition; Targeting; Saccharide recognition; Asialoglycoprotein receptor; Targeting; Hepatocyte; Drug delivery system; PVLA; Dosage form; Styrene polymer; Lactose; Pharmaceutical technology; Pharmacokinetics; Control release polymer
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/0168-3659(94)90169-4

Directed toward pharmacological applications of lactose-carrying polystyrene, (poly ( N-p- vinylben-zyl-O-β- d-galactopyranosyl-(1→ 4)- d-gluconamide ) , PVLA), its body distribution, clearance from blood and specific binding to receptors have been investigated using radiolabelled PVLA. 125I-Labelled PVLA was prepared via copolymerization of N-p- vinylbenzyl-O-β- d-galactopyranosyl-(1 → 4)- d-glu-conamide (VLA) with 10 mol% of 4-(2-propenyl)phenyl acetate followed by radiolabelling of the latter component. When 125I-labelled PVLA was injected into rats through their tail veins, the radio-activity was distributed highly to liver, less to thyroid gland, cecum-large intestine, urine, feces and blood, and much less to lung, heart, kidney, spleen, pancreas, small intestine and urinary bladder. Its concentration to liver was visible by whole-body autoradiography. It was clarified that about 97% of PVLA was distributed to parenchymal liver cells and only 3% to nonparenchymal liver cells. The radioactivity in blood was decreased with time according to a biexponential curve. A two open compartment model is proposed on the basis of the pharmacokinetic analysis of the equation, which elucidated that PVLA migrated rapidly from blood to parenchymal liver cells. Specific binding between 125I-labelled PVLA and asialoglycoprotein receptors on parenchymal liver cells was demonstrated by its inhibition with asialofetuin. The bond dissociation constant estimated by Scatchard analysis was K d= 1.4 × 10 −9 M. The binding was as strong as those of several naturally occurring asialoglycoproteins. These properties of PVLA, as liver-specific targeting materials using galactose ligands as recognition signals to asialoglycoprotein receptors, are discussed with the conformational structures of PVLA which can carry drugs in their hydrophobic regions.