Design of Macromolecular Prodrug Having Antitumor Activity

点击翻译按钮获取中文摘要

5-Fluorouracil (5FU) has a remarkable antitumor activity, which is accompanied, however, by undesirable side-effects. Poly (malic acid), chitosan and polygalactosamine are of interest for application as low or non-toxic, compatible and biodegradable carriers of macromolecular prodrug. In order to provide a macromolecular prodrug of 5FU reducing the side-effects, having affinity for tumor cells and exhibiting strong antitumor activity, the covalent attachment of 5FUs to poly (malic acid) /sa. ccharide, chitosamino-oligosaccharide and polygalactosam ine through hydrophobic methylene spacer groups via urea or ester bonds was carried out.The obtained conjugates were found to be hydrolyzed to release free 5FU itself at 37ﾟC in vitro. These biodegradable polymer/5FU conjugates exhibited strong survival effects against p388 lymphocytic leukemia in mice by intraperitoneal (ip) transiplantation / ip injection in vivo. Moreover, these conjugates did not display any acute toxicity even in the high dose ranges. Poly (malic acid) /5FU /galactosamine and polygalactosamine /5FU exhibited high growth-inhibitory effects against hepatoma cells in vitro th an the other conjugates obtained. Such an appearance of high growth-inhibitory for the conjugate of 5FU/polymer having galactosamine residues against hepatoma cells can be explained by galactose receptor-mediated selective uptake into the hepatoma cells.