Preparation And Self-assembly Behavior Of Novel Chitosan Derivatives

In this paper, poly(ethylene glycol) was grafted onto Chitosan (CS) to improve its solubility in aqueous solution. The self-assembly behavior of the graft copolymer was studied. The main contents are as follows.1. SDS-Chitosan complexes grafted with poly(ethylene glycol) (SCC-g-mPEG) was synthesized by the coupling reaction between isocyanate groups of isocyanate-activated mPEG (mPEG-NCO) and the hydroxyl groups of SCC. The structure of the graft copolymer was characterized by IR and ~1H NMR. The self-assembly behavior of SCC-g-mPEG with different grafting degrees was investigated by fluorescence measurement, dynamic light scattering (DLS) and transmission electron microscopy (TEM) techniques. Naproxen was chosen as a model drug to prepare drug-loaded micelles. The morphology of drug-loaded micelles was characterized by DLS and TEM. Ultraviolet (UV) spectroscopy measurement was used to determine the drug loading efficiency. The results reveal that SCC-g-PEG can self-assemble into nano-sized spherical micelles. The grafting degree of PEG can affect the particle size of micelles.2. The bromized SCC (Br-SCC) was synthesized by conjugating 2~bromo-2-methyl propiomc acid to the hydroxyl groups of SCC which was used as an organo-soluble precursor in this study. Br-SCC was used as a macromolecular ATRP initiator to polymerize methyl ether poly(ethylene glycol) methacrylate (MPEGMA) using copper(I) bromide/bipyridine as a catalyst, yielding SCC-O-MPEGMA. SDS was removed from the product by precipitating SCC-O-MPEGMA solution into aqueous trihydroxymethylamine (Tris) medium. The chemical structure of the intermediate and CS-O-MPEGMA was studied by FT-IR and ~1H NMR. Complexation behaviors between CS-O-MPEGMA and heparin were studied by dynamic light scattering, zeta potential analyzer and TEM. CS-O-MPEGMA which could be conveniently synthesized according to the scheme proposed in this study has well-defined chemical structure. The grafting of MPEGMA has no effect on the cationic density of the final product. In addition, the copolymers could form spherical micelles with anionic agents. The above characteristics of CS-O-MPEGMA make it promising for tumor targeting and gene delivery.