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.
Department of Applied Chemistry, Faculty of Engineering, Kansai University, Osaka, Japan.
Y
Y
Ohya
T
T
Takei
H
H
Kobayashi
T
T
Ouchi
D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D002686:Chitin / Q000031:analogs & derivatives* / Q000737:chemistry; D048271:Chitosan; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D005472:Fluorouracil / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D005685:Galactans / Q000737:chemistry; D005782:Gels; D006801:Humans; D037102:Lectins; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008863:Microspheres; D011134:Polysaccharides / Q000737:chemistry*; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured
D003692:Delayed-Action Preparations; D005685:Galactans; D005782:Gels; D037102:Lectins; D011134:Polysaccharides; D002686:Chitin; C079948:6-O-carboxymethyl-N-acetyl-1,4-polygalactosamine; D048271:Chitosan; D005472:Fluorouracil