Reduction-sensitive Nanocarriers Based Chitosan For Drug Delviery

In this study, chitosan was carried on hydrophobic modification to generate a novel amphiphilic graft copolymer, in order to develop a kind of redox-sensitive nanocarriers for drug delivery. Micelles’self-assembly behavior, and changes of micelles’morphology in reducing environment, and anti-cancer drug release behaviour were studied, main contents were as follows:An amphiphilic graft copolymer named glycidol chitosan-S-S-polycaprolactone (GC-S-S-PCL) was synthesized through many steps. The main chain was the reaction product between chitosan and glycidol which had perfect solubility in water and organic solvent, and the hydrophobic chain was PCL, which was linked to the main chain by a disulfide bond. The physicochemical properties of GC-S-S-PCL were characterized by FT-IR, TEM, and1H-NMR. GC-S-S-PCL can form spherical micelles by self-assembly in water solutions with small size, which were characterized by FL with pyrene molecular probe, DLS, and TEM.The impacts of different DTT concentration and mediun pH on the micelles structure and morphology of blank and drug-loaded micelles were also elaborately investigated. Changes of drug-(un)loaded micelles structure and other properties were characterized by DLS, TEM, FL, UV-vis. The result shows that the medium pH could influence the reduction sensitivity of graft copolymers, the micelles had some certain reduction sensitivity when the medium pH=7.4, but when the medium was changed to pH5.0, the sensitivity was significantly inhibited because of the disapperance activity of DTT.The poor soluble anticancer drug, doxorubicin (DOX), was loaded into GC-S-S-PCL micelles, and the drug release behaviour and antitumor activity were investigated. The results showed that drug release had certain redox sensitivity in pH7.4. What’s more, drug release behaviour still had good enzyme sensitivity that could be accelerated by the lysozyme in the medium. The antitumor efficacy were also studied using human liver carcinoma cell line (HepG2), which showed that the blank micelles had excellent biocompatibility, the glutathione in the medium can improve the cell toxicity of drug-loaded micelles.