Synthesis And Characterization Of Envirment-sensitive Diblock Copolymer Of Based On HEC

Polymer micelles have been intensively investigated in every fields of biomedicine. They enjoy several advantages over other particulate configurations, which include low critical micelle concentration(cmc) that render the drug-loaded micelles stable in the blood stream to achieve long-circulating time, bio-compatibility, etc. Self-assembly of amphiphilic copolymers has been widely used to prepare the nano-sized micelles in water where the hydrophobic block forms the core and the hydrophilic one forms the shell. In this thesis, we prepared a series of temperature-sensitive and pH-sensitive hydrophilic block copolymers by coupling of cellulose ether-hydroxyethyl cellulose (HEC) ( M w =9×104) , which is water-soluble and biodegradable, with amino-terminated poly(N-isopropylacrylamide) and polyacrylic acid, respectively. The nanometer micelles were prepared by changing the temperature or pH value of these copolymer aqueous solutions.(1) The amino-terminated poly(N-isopropylacrylamide) (PNIPAAm-NH2) and amino-terminated polyacrylic acid (PAA-NH2) were prepared by free radical polymerization using 2-aminoethanethiol as a chain transfer agent. The double-hydrophilic HEC-b-PNIPAAm and HEC-b-PAA copolymer were synthesized with reducing agent NaCNBH3 by coupling of HEC with amino-terminated poly(N-isopropylacrylamide) (PNIPAAm-NH2) and amino-terminated polyacrylic acid (PAA-NH2), respectively. The structure of copolymers was characterized by FTIR and NMR spectra. The molecular weight of HEC and copolymers were measured by GPC. The results indicated that the HEC-b-PNIPAAm and HEC-b-PAA block copolymers were successfully prepared.(2) The solution behavior of HEC-b-PNIPAAm copolymer was investigated by UV spectrometer, diffraction scanning calorimetry (DSC), fluorescence spectrum (FS) and surface tension instrument (ST). The thermo-sensitive micellization of HEC-b-PNIPAAm was found. The lower critical solution temperature (LCST) of HEC-b-PNIPAAm was ~33oC and was similar with the LCST of pure PNIPAAm-NH2. The critical micillization concentration (CMC) of HEC-b-PNIPAAm copolymer was measured by FS and ST and the result was about 0.22mg/ml. When the temperature was above the LCST of HEC-b-PNIPAAm, the copolymer aggregated. The micelles were investigated by transmission electron microscopy (TEM) and it was found the morphology of these micelles was rod-like and their average size was ~100nm.(3) The rheological behavior of HEC and HEC-b-PNIPAAm in water was investigated by rheometer. HEC solution was a expand fluid in the range of the experimental shear rate. Whereas the HEC-b-PNIPAAm solution was a Newton fluid when the concentration was lower and became a non-Newton fluid when the concentration was higher.(4) HEC-b-PAA aqueous solution was investigated by UV, DSC, FS and ST. The pH-sensitive micellization of HEC-b-PAA was found. The critical micellization pH value of HEC-b-PAA was about 3.5. The CMC of HEC-b-PAA copolymer was found ~0.20mg/ml.