Comparison of the liver subcellular distribution of free daunomycin and that bound to galactosamine targeted N-(2-hydroxypropyl)methacrylamide copolymers, following intravenous administration in the rat

Wedge, S. R.; Duncan, Ruth; Kopečková, Pavla

doi:10.1038/bjc.1991.128

Cited by 33 publications

(18 citation statements)

References 27 publications

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“…Their clearance from the bloodstream was related to the N -acylated galactosamine content (1–11 mol%) of the HPMA copolymer [57–59]. Separation of the rat liver into hepatocytes and non-parenchymal cells indicated that the polymer is largely associated with hepatocytes, and density-gradient subcellular fractionation of the liver confirmed that the HPMA copolymers were internalized by liver cells and transported, with time, into the secondary lysosomes [59,60]. It was very important to find that HPMA copolymers containing side-chains terminated in galactosamine and anticancer drug adriamycin also preferentially accumulated in the liver, i.e., it appeared that non-specific hydrophobic interactions with cell membranes did not interfere with the biorecognition by hepatocytes [61].…”

Section: Originsmentioning

confidence: 99%

HPMA copolymers: Origins, early developments, present, and future☆

Kopeček

Kopečková

2010

Advanced Drug Delivery Reviews

536

428

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The overview covers the discovery of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers, initial studies on their synthesis, evaluation of biological properties, and explorations of their potential as carriers of biologically active compounds in general and anticancer drugs in particular. The focus is on the research in the authors' laboratory -the development of macromolecular therapeutics for the treatment of cancer and musculoskeletal diseases. In addition, the evaluation of HPMA (co)polymers as building blocks of mod and new biomaterials is presented: the utilization of semitelechelic poly(HPMA) and HPMA copolymers for the modification of biomaterial and protein surfaces and the design of hybrid block and graft HPMA copolymers that self-assemble into smart hydrogels. Finally, suggestions for the design of second-generation macromolecular therapeutics are portrayed.

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Section: Originsmentioning

confidence: 99%

HPMA copolymers: Origins, early developments, present, and future☆

Kopeček

Kopečková

2010

Advanced Drug Delivery Reviews

536

428

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“…Carriers have included asialoglycoproteins of natural origin, synthesized neoglycoproteins, and synthetic polymers modified to contain galactose residues (2)(3)(4)(5)(6). Another approach in the design of carriers binding the asialoglycoprotein receptor involves the synthesis of low molecular weight compounds containing multiple galactose residues (7,8).…”

Section: Introductionmentioning

confidence: 99%

Arabinogalactan for Hepatic Drug Delivery

Groman¹,

Enriquez²,

Jung³

et al. 1994

Bioconjugate Chem.

112

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Arabinogalactan, a polysaccharide from the tree Larix occidentalis, has been purified and its biological and physical properties described. Intravenous injection of radiolabeled arabinogalactan (4 mg/kg) in rats resulted in 52.5% of the dose being present in the liver, while prior injection of asialofetuin (100 mg/kg) reduced hepatic radioactivity to 3.54%. Gel chromatography indicates arabinogalactan is a single species of 19 kDa, while light scattering gave a molecular weight of 40 kDa. Glycosyl linkage analysis of arabinogalactan is consistent with a highly branched structure comprising a backbone of 1,3-linked galactopyranose connected by 1,3-glycosidic linkages, comprised of 3,4,6-,3,6-, and 3,4- as well as 3-linked residues. In the carbon-13 NMR spectra, the major resonances of arabinogalactan are assigned to beta-galactopyranose, beta-arabinofuranose, and beta-arabinopyranose. Arabinogalactan produced no adverse reactions in single intravenous dose (mouse, 5000 mg/kg) and repeat dose toxicity studies (rats, 500 mg/kg/day, 90 days). When tritiated arabinogalactan was injected, radioactivity cleared from the liver with a half-life of 3.42 days. Arabinogalactan has properties that make it suitable as a carrier for delivering diagnostic or therapeutic agents to hepatocytes via the asialoglycoprotein receptor.

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“…In contrast, the control copolymer was hardly accumulated in the liver (Figure 2). 94 Separation of the rat liver into hepatocytes and non‐parenchymal cells indicated that the polymer was mainly associated with hepatocytes, and density‐gradient subcellular fractionation of the liver confirmed that the HPMA copolymers were internalized by liver cells and transported, with time, into the secondary lysosomes.…”

Section: Hpma Copolymer–drug Conjugates For Cancer Therapymentioning

confidence: 93%

Carbohydrate‐based Biomedical Copolymers for Targeted Delivery of Anticancer Drugs

David

2010

Israel Journal of Chemistry

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A variety of strategies and carrier molecules have been used to direct therapeutic agents to tumor sites. The incorporation of a specific targeting moiety to drug carrier may result in active drug uptake by malignant cells. Carbohydrates are important mediators of cell–cell recognition events and have been implicated in related processes such as cell signaling regulation, cellular differentiation, and immune response. The biocompatibility of carbohydrates and their ability to be specifically recognized by cell‐surface receptors indicate their potential utility as ligands in targeted drug delivery for therapeutic applications. Yet, carbohydrates are not ideal targeting ligands because they are difficult to synthesize, bind weakly to carbohydrate receptors, and are prone to suffer from enzyme degradation due to labile glycosidic linkages. This review describes the design and development of HPMA‐based biomedical copolymers to facilitate the selective delivery of drugs to tumor tissues via carbohydrate–endogenous lectin interactions. Various carbohydrate‐decorated HPMA copolymer–drug conjugates are presented and the application of the copolymers for drug delivery is discussed. Current efforts to increase the affinity of carbohydrate ligands for their target receptors through multivalent display are also discussed. These novel HPMA copolymer carbohydrate conjugates hold promise as clinically relevant drug delivery systems for cancer therapy.

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Comparison of the liver subcellular distribution of free daunomycin and that bound to galactosamine targeted N-(2-hydroxypropyl)methacrylamide copolymers, following intravenous administration in the rat

Cited by 33 publications

References 27 publications

HPMA copolymers: Origins, early developments, present, and future☆

HPMA copolymers: Origins, early developments, present, and future☆

Arabinogalactan for Hepatic Drug Delivery

Carbohydrate‐based Biomedical Copolymers for Targeted Delivery of Anticancer Drugs

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