Preparation And Characterization Of 5-Fluorouracil-loaded Chitosan Nanoparticles.

Chitosan(CS) is a natural cationic polysaccharide.As a biocompatible and slowly degradable polymer, chitosan has been widely used in drug delivery systems especially in drug-controlled release, targeting, and intellectualized delivery systems. In order to improve the treatment efficacy and reduce the side effect of 5-Fluorouracil (5-Fu), 5-Fu as model drug and the sustained-releaser of targeted 5-Fu-loaded nanoparticles has been attracted much attention in the field of drug controlled release.This subject was to explore the methods of coupling the antitumor drugs 5-Fu to CS based on ionic gelation process of tripolyphosphate (TPP) and CS, and provide references for the study of targeting, sustained and controlled release delivery systems of antitumor drugs. In order to gain the best parameters for preparing nanoparticles, the influences of different factors on average drug loading and average incorporation efficiency of nanoparticles were evaluated by orthogonal-designing method using L₁₆(4⁵) table. The physicochemical properties of nanoparticles were investigated in detail by using XRD,FT-IR, UV-Vis spectra, transmissing electron microscope(TEM), Zeta potential analysis, atomic force microscope(AFM) and laser dynamic scattering. The preparation mechanisms of the nanoparticles were discussed. The average particle size of the nanoparticles was 180-280 nanometers. The average drug loading and the average incorporation efficiency were 24.9%, 44.0% respectively.Drug releasing property of 5-Fu/CS nanoparticles was studied and the drug releasing performance was good. The 5-Fu from nanoparticles in vitro could be described double phase dynamic model and could be described by the following equation: Q=-0.122+31.75*(1-e^-t/0.293) +191.19*(1-e^-t/418.32).The inhibitory of the nanoparticles to the two tumor cells were determined with the method of MTT. And the two tumor cell lines were sensitive to the nanoparticles,the cytoxidties were positive interrelated with reaction time and the logreleased dose.The morphoy of membrane surface ultrastructures of human lungcarcinomacarcinoma GLC-82 cells,human hepatocarcinoma cells strain BEL7402 were observed and compared by atomic force microscopy. At the same time,the effect of 5-Fu and 5-Fu/CS nanoparticles on the membrane surfaces of BEL7402 cell and GLC-82 cell were studied.We found that there are distinct differences of membrane surface ultrastrures among tumor cells between normal BEL7402 and GLC-82 cells and drug-administrated ones.