RELEASE BEHAVIOR OF 5-FLUOROURACIL FROM CHITOSAN-GEL NANOSPHERES IMMOBILIZING 5-FLUOROURACIL COATED WITH POLYSACCHARIDES AND THEIR CELL-SPECIFIC CYTOTOXICITY
Y. Ohya et al., RELEASE BEHAVIOR OF 5-FLUOROURACIL FROM CHITOSAN-GEL NANOSPHERES IMMOBILIZING 5-FLUOROURACIL COATED WITH POLYSACCHARIDES AND THEIR CELL-SPECIFIC CYTOTOXICITY, Pure and applied chemistry, A31(5), 1994, pp. 629-642
Small-sized chitosan-gel nanospheres, CNSs (average diameter 250 nm),
containing 5-fluorouracil (5FU) or immobilizing 5FU derivatives (amino
pentyl-carbamoyl-5FU or aminopentyl-ester-methylene-5FU) were prepared
by the glutaraldehyde crosslinking technique and the emulsion method.
When chitosan was crosslinked with glutaraldehyde, these 5FU derivati
ves were simultaneously immobilized to CNSs by means of Schiff's base
formation. The CNSs were coated with anionic polysaccharides, such as
boxymethyl-N-acetyl-alpha-1,4-polygalactosamine/Na (CM-NAPGA/Na), 6-O-
carboxymethyl-chitin/Na (CM-chitin/Na), and sodium hyaluronate, throug
h formation of a polyelectrolyte complex membrane to give CNS/polyanio
n, i.e., CNS/G, CNS/C, and CNS/H, respectively. The polyelectrolyte co
mplex of polysaccharide was employed to achieve the controlled release
and effective targeting of 5FU by the CNSs. The release rate of 5FU f
rom the CNSs could be controlled by immobilization of 5FU, degree of d
eacetylation of chitosan used and coating with polysaccharides. Since
very few galactosamine residues are known to be able to cross-react wi
th ligands for galactose, the galactosamine residues on the surface of
CNS/Gs are expected to act as the targeting moieties for hepatocyte.
The CNS/G showed the lectin mediated aggregation phenomenon by the add
ition of APA lectin. Moreover, CNS/G had the highest cytotoxic activit
y among the three kinds of CNS/polyanion and CNS in HLE human hepatoma
cell culture system in vitro.