Online citations, reference lists, and bibliographies.
← Back to Search

Synthesis And Pharmacokinetics Of A New Liver-Specific Carrier, Glycosylated Carboxymethyl-Dextran, And Its Application To Drug Targeting

M. Nishikawa, Akiko Kamijo, T. Fujita, Y. Takakura, H. Sezaki, M. Hashida
Published 2004 · Chemistry, Medicine

Cite This
Download PDF
Analyze on Scholarcy
Share
To develop a new carrier system for hepatic targeting, carboxymethyl-dextran (CMD) was modified with galactose and mannose residues (Gal-CMD, Man-CMD), and their disposition characteristics were studied in mice using 14C-labeled dextran. At a dose of 1 mg/kg, i.v.-injected Gal-CMD and Man-CMD rapidly accumulated in the liver parenchymal and nonparenchymal cells, respectively, because of their preferential uptake via carbohydrate receptors in these cells. Pharmacokinetic analysis revealed that their uptake rates were sufficiently large for selective drug targeting. Targeting of cytosine β-D-arabinoside (araC) was studied using Gal-CMD as a specific carrier to the hepatocytes. From the conjugate of araC with Gal-CMD, araC was released with a half-life of 36 hr in phosphate buffer (pH 7.4) and 23 hr in plasma. An in vivo biodistribution study demonstrated a disposition profile of the conjugated araC similar to that of the carrier, and selective delivery to hepatocytes of up to 80% of the dose was achieved. These findings suggest that glycosylated CMDs are carriers with a high affinity to liver parenchymal or nonparenchymal cells without any affinity to other tissues.
This paper references
10.1089/CDD.1987.4.145
Conjugates of ara-AMP with lactosaminated albumin: a study on their immunogenicity in mouse and rat.
L. Fiume (1987)
Hepatic endocytosis of various types of mannose-terminated albumins. What is important, sugar recognition, net charge, or the combination of these features.
R. W. Jansen (1991)
10.1016/0014-5793(86)80742-6
Galactosylated poly(L‐lysine) as a hepatotropic carrier of 9‐β‐D‐arabinofuranosyladenine 5'‐monophosphate
L. Fiume (1986)
10.1002/9780470122860.CH3
The role of surface carbohydrates in the hepatic recognition and transport of circulating glycoproteins.
G. Ashwell (1974)
Disposition and pharmacokinetics of a polymeric prodrug of mitomycin C, mitomycin C-dextran conjugate, in the rat.
M. Hashida (1984)
Preparation of oestriol-6-(O-carboxymethyl) oxime and oestrone-6-(carboxymethyl) oxime-bovine serum albumin conjugates.
P. Dean (1972)
10.1016/0378-5173(87)90019-6
Development of a novel polymeric prodrug of mitomycin C, mitomycin C-dextran conjugate with anionic charge. II. Disposition and pharmacokinetics following intravenous and intramuscular administration
Y. Takakura (1987)
10.1023/A:1015807119753
Disposition Characteristics of Macromolecules in Tumor-Bearing Mice
Y. Takakura (2004)
10.1023/A:1016489002393
Disposition and Tumor Localization of Mitomycin C–Dextran Conjugates in Mice
Y. Takakura (2004)
10.1007/978-1-4684-4862-7_1
Drug Targeting in Human Cancer Chemotherapy
Y. Schneider (1984)
10.1111/j.2042-7158.1992.tb03632.x
Demonstration of the Receptor‐mediated Hepatic Uptake of Dextran in Mice
M. Nishikawa (1992)
10.1023/A:1015961424122
Covalent and Noncovalent Protein Binding of Drugs: Implications for Hepatic Clearance, Storage, and Cell-Specific Drug Delivery
D. Meijer (2004)
10.1016/0006-2952(87)90388-1
Covalent linkage of carboxypeptidase G2 to soluble dextrans--II. In vivo distribution and fate of conjugates.
R. Melton (1987)
10.1016/0006-2952(65)90175-9
Studies of the enzymatic deamination of cytosine arabinoside. I. Enzyme distribution and species specificity.
G. W. Camiener (1965)
10.1016/0016-5085(84)90185-9
Hyperasialoglycoproteinemia in patients with chronic liver diseases and/or liver cell carcinoma. Asialoglycoprotein receptor in cirrhosis and liver cell carcinoma.
T. Sawamura (1984)
10.1016/0169-409X(89)90012-4
Biodegradable soluble macromolecules as drug carriers
J. Drobník (1989)
10.1016/0006-291X(81)91644-2
cis-Aconityl spacer between daunomycin and macromolecular carriers: a model of pH-sensitive linkage releasing drug from a lysosomotropic conjugate.
W. Shen (1981)
10.1016/0014-5793(80)80639-9
Selective inhibition of ectromelia virus DNA synthesis in hepatocytes by adenine‐9‐β‐D‐arabinofuranoside (ara‐A) and adenine‐9‐β‐D‐arabinofuranoside 5′‐monophosphate (ara‐AMP) conjugated to asialofetuin
L. Fiume (1980)
10.1016/0169-409X(89)90013-6
Soluble macromolecular carriers for the delivery of antitumour drugs
H. Sezaki (1989)
10.1172/JCI110573
Modulation of a glycoprotein recognition system on rat hepatic endothelial cells by glucose and diabetes mellitus.
J. Summerfield (1982)
10.1002/cpt1971126944
Clinical pharmacology of l‐β‐D‐arabinofuranosyl cytosine
D. V. Ho (1971)
10.1042/BJ1920597
The role of extra-hepatic tissues in the receptor-mediated plasma clearance of glycoproteins terminated by mannose or N-acetylglucosamine.
P. Schlesinger (1980)
10.1021/BI00663A008
2-Imino-2-methoxyethyl 1-thioglycosides: new reagents for attaching sugars to proteins.
Y. Lee (1976)
10.1038/bjc.1988.31
Anticancer agents coupled to N-(2-hydroxypropyl)methacrylamide copolymers. II. Evaluation of daunomycin conjugates in vivo against L1210 leukaemia.
R. Duncan (1988)
Antitumor activity of 1-beta-D-arabinofuranosylcytosine conjugated with polyglutamic acid and its derivative.
Y. Kato (1984)
10.1016/0168-8278(91)90073-K
Asialoglycoprotein receptor in human isolated hepatocytes from normal liver and its apparent increase in liver with histological alterations.
C. Eisenberg (1991)
10.1016/0006-2952(86)90084-5
Drug targeting in antiviral chemotherapy. A chemically stable conjugate of 9-beta-D-arabinofuranosyl-adenine 5'-monophosphate with lactosaminated albumin accomplishes a selective delivery of the drug to liver cells.
L. Fiume (1986)
10.1146/ANNUREV.BI.51.070182.002531
Carbohydrate-specific receptors of the liver.
G. Ashwell (1982)
10.1073/PNAS.79.2.626
A covalent linkage between daunorubicin and proteins that is stable in serum and reversible by lysosomal hydrolases, as required for a lysosomotropic drug-carrier conjugate: in vitro and in vivo studies.
A. Trouet (1982)
Tc-99m galactosyl-neoglycoalbumin: in vitro characterization of receptor-mediated binding.
D. Vera (1984)
10.1016/0076-6879(72)28018-1
[16] Carbohydrate antigens: Coupling of carbohydrates to proteins by diazonium and phenylisothiocyanate reactions
C. R. McBroom (1972)
10.1016/0169-409X(89)90037-9
Receptor-mediated delivery of drugs to hepatocytes
R. Fallon (1989)
A histochemical study of the distribution and fate of dextran in tissues of the mouse.
Mowry Rw (1953)
10.1016/0006-2952(89)90007-5
Selective delivery of drugs to macrophages through a highly specific receptor. An efficient chemotherapeutic approach against leishmaniasis.
G. Chaudhuri (1989)
10.1016/0304-4165(84)90320-9
Tyrosinamide residues enhance pinocytic capture of N-(2-hydroxypropyl)methacrylamide copolymers.
R. Duncan (1984)
10.1016/0378-5173(92)90136-P
Pharmacokinetics of receptor-mediated hepatic uptake of glycosylated albumin in mice
M. Nishikawa (1992)
10.1002/JSS.400130107
The scavenger cell pathway for lipoprotein degradation: specificity of the binding site that mediates the uptake of negatively-charged LDL by macrophages.
M. Brown (1980)
Targeted delivery of human recombinant superoxide dismutase by chemical modification with mono- and polysaccharide derivatives.
T. Fujita (1992)
10.1016/0169-409X(89)90006-9
Dextran prodrugs — structure and stability in relation to therapeutic activity
C. Larsen (1989)
10.1016/0169-409X(89)90036-7
Macrophages as targets for drug delivery
S. Gordon (1989)



This paper is referenced by
10.1007/BF02353518
Pharmacokinetic considerations of regional administration and drug targeting: Influence of site of input in target tissue and flux of binding protein
M. Rowland (2006)
10.2165/00003088-200241100-00002
Clinical Pharmacokinetics of Cytarabine Formulations
A. Hamada (2002)
10.1163/156856202320813846
Synthesis and biological properties of antitumor-active conjugates of ADR with dextran
Jan-An Guu (2002)
10.1023/A:1016053128569
Development and Pharmacokinetics of Galactosylated Poly-L-Glutamic Acid as a Biodegradable Carrier for Liver-Specific Drug Delivery
Hideki Hirabayashi (2004)
10.1517/17425247.2012.673580
Dextran conjugates in drug delivery
J. Varshosaz (2012)
10.1002/JPS.10476
Synthesis and in vitro evaluation of potential anti-leishmanial targeted drugs of pyrimethamine.
P. B. De Carvalho (2003)
10.23860/diss-agarwal-hitesh-2008
Design and Evaluation of Nucleoside Derivatives for Targeted Drug Delivery and Therapeutic Applications
H. Agarwal (2008)
10.1016/J.IJPHARM.2004.08.021
Uptake characteristics of mannosylated and fucosylated bovine serum albumin in primary cultured rat sinusoidal endothelial cells and Kupffer cells.
Y. Higuchi (2004)
10.1002/APP.21975
Synthesis and characterization of chitosan derivatives carrying galactose residues
Can Zhang (2005)
10.1080/02652048.2016.1185474
Doxorubicin-loaded galactose-conjugated poly(d,l-lactide-co-glycolide) nanoparticles as hepatocyte-targeting drug carrier
M. Margarida Cardoso (2016)
10.18520/CS/V112/I02/390-395
Biocompatibility of Synthetic and Bio-Material Fusion
D. Pant (2017)
10.1517/17425240802622096
Nanoparticles for human liver-specific drug and gene delivery systems: in vitro and in vivo advances
T. Kasuya (2009)
10.1111/j.1440-1681.2006.04408.x
POLYMERIC CORE‐SHELL NANOPARTICLES FOR THERAPEUTICS
Y. Yang (2006)
10.1016/j.addr.2020.06.015
Role of pharmacokinetic consideration for the development of drug delivery systems: A historical overview.
M. Hashida (2020)
10.1093/rb/rby023
Re-evaluating the importance of carbohydrates as regenerative biomaterials
Heidi F. Oldenkamp (2019)
10.1023/A:1016084508097
Macromolecular Carrier Systems for Targeted Drug Delivery: Pharmacokinetic Considerations on Biodistribution
Y. Takakura (2004)
10.1016/S0378-5173(03)00128-5
Development of polymeric nanoparticulate drug delivery systems: evaluation of nanoparticles based on biotinylated poly(ethylene glycol) with sugar moiety.
I. Kim (2003)
10.1016/J.IJPHARM.2005.02.027
Cellular recognition of paclitaxel-loaded polymeric nanoparticles composed of poly(gamma-benzyl L-glutamate) and poly(ethylene glycol) diblock copolymer endcapped with galactose moiety.
Y. Jeong (2005)
10.1248/YAKUSHI.127.797
[Bio-nanocapsules for in vivo pinpoint drug delivery].
J. Jung (2007)
Selective targeting of the anti-viral agent lamivudine to the liver
Krishna C Chimalakonda (2007)
10.1016/J.REACTFUNCTPOLYM.2012.06.019
Preparation and characterization of polymeric nanoparticles composed of poly(dl-lactide-co-glycolide) and poly(dl-lactide-co-glycolide)-co-poly(ethylene glycol)-10%-Triblock end-capped with a galactose moiety
I. N. Peça (2012)
10.1023/A:1018979515073
Structural Requirements for Alkylglycoside-Type Renal Targeting Vector
K. Suzuki (2004)
10.1016/B978-0-323-46144-3.00004-0
Improving chemotherapy drug delivery by nanoprecision tools
Nehal A. Salahuddin (2017)
10.1590/S1516-93322005000200004
Latenciação e formas avançadas de transporte de fármacos
M. C. Chung (2005)
Frontiers in Research Review: Cutting-Edge Molecular Approaches to Therapeutics POLYMERIC CORE-SHELL NANOPARTICLES FOR THERAPEUTICS
Y. Yang (2006)
10.1016/J.JCONREL.2007.10.007
Mannosylated semiconductor quantum dots for the labeling of macrophages.
Y. Higuchi (2008)
10.1021/acsnano.6b02878
Efficient Targeting of Adipose Tissue Macrophages in Obesity with Polysaccharide Nanocarriers.
L. Ma (2016)
10.1038/nbt798
Synthesis of a poly(vinylpyrrolidone-co-dimethyl maleic anhydride) co-polymer and its application for renal drug targeting
H. Kamada (2003)
10.1002/cmdc.201600374
Half‐Life Extension of Biopharmaceuticals using Chemical Methods: Alternatives to PEGylation
Søren B van Witteloostuijn (2016)
10.1533/9781845694814.1.3
Polysaccharides as carriers of bioactive agents for medical applications
R. Pawar (2008)
10.1016/j.jconrel.2014.06.001
Glycosylation-mediated targeting of carriers.
S. Kawakami (2014)
10.1007/978-3-030-29168-6_12
Asialoglycoprotein Receptor and Targeting Strategies
S. Das (2019)
See more
Semantic Scholar Logo Some data provided by SemanticScholar