Water-soluble polysaccharide-anthracycline conjugates: biological activity.
The anticancer agents doxorubicin and daunorubicin were covalently linked to the water-soluble anionic polysaccharides hyaluronic acid and carboxy-methylcellulose. The drug-polymer conjugates are in principle prevented from entering cells, can efficiently bind to cell surfaces and allow precise dose-response determinations. In addition, they are not able to bind DNA because of their negative charge. Cell growth and DNA synthesis inhibition studies indicated decreased cell toxicity for the polymer conjugates. The mol. wt of the carrier was shown to affect the biological activity of the anthracycline to a moderate extent. Partial drug incorporation into cells was observed as a function of time, probably due to endocytosis phenomena followed by biochemical cleavage of the conjugate. The conclusion was drawn that membrane binding appears to contribute to total toxicity only to a minor extent.
Cera
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Department of Pharmaceutical Sciences, Centro Studi sulla Chimica del Farmaco e dei Prodotti Biologicamente Attivi, Padova, Italy.
Palumbo
M
M
Stefanelli
S
S
Rassu
M
M
Palù
G
G
D002266:Carboxymethylcellulose Sodium / Q000378:metabolism / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000187:drug effects; D003630:Daunorubicin / Q000378:metabolism / Q000494:pharmacology*; D004317:Doxorubicin / Q000378:metabolism / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism / Q000494:pharmacology*; D008854:Microscopy, Electron; D014407:Tumor Cells, Cultured
D004317:Doxorubicin; D006820:Hyaluronic Acid; D004247:DNA; D002266:Carboxymethylcellulose Sodium; D003630:Daunorubicin