Release behaviour of 5-fluorouracil from chitosan-gel microspheres immobilizing 5-fluorouracil derivative coated with polysaccharides and their cell specific recognition.

In order to provide a device releasing drugs in a controlled manner and having targetability to specific organs or cells, chitosan-gel microspheres, CMS, crosslinked with glutaraldehyde, immobilizing 1-[N-(5-aminopentyl) carbamoyl]-5-fluorouracil, 1, coated with anionic polysaccharides, such as 6-O-carboxymethyl-N-acetyl-alpha-1,4-polygalactosamine (CM-NAPGA), 6-O-carboxymethyl-chitin, alginic acid and heparin, by polyelectrolyte complex membrane formation were prepared. When chitosan was crosslinked with glutaraldehyde, 1 was simultaneously immobilized into CMS by Schiff's base formation. Average diameter of CMS obtained was estimated to be about 0.5-1.0 micron by SEM observation. In physiological saline media, only free 5-FU was released from the CMS but 1 and any 5-FU derivative was not. Release rate of 5-FU from the CMS was reduced by coating with polyelectrolyte complex membrane of cationic chitosan and anionic polysaccharides. CMS coated with CM-NAPGA showed a lectin-mediated specific aggregation phenomenon by addition of Abrus precatorius agglutinin. Moreover, the CMS immobilizing 1 coated with CM-NAPGA showed higher growth-inhibitory effect against SK-Hep-1 (human hepatoma) cells in vitro than the CMS coated with other polysaccharides.