FATE OF GLYCOSYLATED DEXTRANS AFTER INVIVO ADMINISTRATION

被引：26

作者：

VANSTEENKISTE, S ^{[1
]}

SCHACHT, E ^{[1
]}

DUNCAN, R ^{[1
]}

SEYMOUR, L ^{[1
]}

PAWLUCZYK, I ^{[1
]}

BALDWIN, R ^{[1
]}

机构：

[1] STATE UNIV GHENT,ORGAN CHEM LAB,B-9000 GHENT,BELGIUM

来源：

JOURNAL OF CONTROLLED RELEASE | 1991年 / 16卷 / 1-2期

关键词：

DEXTRAN; GLYCOSYLATION; TARGETING; RECEPTOR BLOCKING; IMMUNOTOXIN;

D O I：

10.1016/0168-3659(91)90033-A

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Polymers bearing galactose or mannose residues accumulate in the liver after intravenous administration to rat or mice. In this study dextrans carrying D-galactose residues were injected intravenously in rat. Their rates of blood clearance and body distribution were measured. D-Galactosylated polymers were cleared more rapidly in comparison with non-glycosylated control polymer. The former are more easily captured by the liver. Dextran substituted with tri-D-galactose units was cleared faster than mono-D-galactose substituted dextran. Introduction of FITC groups in dextran or D-galactosylated dextran (D.S.: 0.7%) resulted in a faster internalization by the liver. The effect of the galactose co-substituents was overridden by that of the FITC-moieties. D-Mannosylated dextran was evaluated as a blocker of liver D-mannose receptors. It was shown that co-administration of D-mannosylated dextran to i.v. administered ricin A immunotoxin significantly decreased the rate of blood clearance and liver uptake of the immunotoxin. Body distribution experiments carried out at 24 h indicated the liver blocking to be transient.

引用

页码：91 / 99

页数：9

共 42 条

[1]

Morell, Irvin, Sternlieb, Scheinberg, Ashwell, Physical and chemical studies on ceruloplasmin. Metabolic studies on sialic acid free ceruloplasmin in vivo, J. Biol. Chem., 243, pp. 155-159, (1968)

[2]

Monsigny, Kieda, Roche, Membrane lectins, Biol. Cell, 36, pp. 289-303, (1979)

[3]

Monsigny, Kieda, Roche, Membrane glycoproteins, glycolipids and membrane lectins as recognition signals in normal and malignant cells, Biol. Cell, 47, pp. 95-110, (1983)

[4]

Monsigny, Roche, Midoux, Uptake of neoglycoproteins via membrane lectin(s) of L 1210 cells evidenced by quantitative flow cytofluorometry and drug targeting, Biol. Cell, 51, pp. 187-196, (1984)

[5]

Schwartz, The hepatic asialoglycoprotein receptor, C.R.C. Crit. Rev. Biochem., 16, pp. 207-233, (1984)

[6]

Ashwell, Harford, Carbohydrate specific receptors of the liver, Ann. Rev. Biochem, 51, pp. 531-554, (1982)

[7]

Stowell, Lee, The binding of d-glucosylneoglycoproteins to the hepatic asialoglycoprotein receptor, J. Biol. Chem, 253, pp. 6107-6110, (1978)

[8]

Duncan, Kopecek, Rejmanova, Lloyd, Targeting of N-(2-hydroxypropyl) methacrylamide copolymers to liver by incorporation of galactose residues, Biochim. Biophys. Acta, 755, pp. 518-521, (1983)

[9]

Duncan, Seymour, Scarlett, Lloyd, Rejmanova, Kopecek, Fate of N-hydroxypropyl)-methacrylamide copolymers with pendent galactosamine residues after intravenous administration to rats, Biochim. Biophys. Acta, 880, pp. 62-71, (1986)

[10]

Kopecek, Duncan, Targetable polymeric prodrugs, Journal of Controlled Release, 6, pp. 315-327, (1987)

← 1 2 3 4 5 →