Preparation and antioxidant activity of PEGylated chitosans with different particle sizes

The preparation of water-soluble chitosans such as polyethylene glycol (PEG)-grafted derivatives is essential for improving the biocompatibility and water solubility of these types of polysaccharides. In this study, chitosans (CS1; 22 kDa, CS2; 38 kDa, CS3; 52 kDa) with different molecular weights were modified with a succinyl ester derivative of monomethoxypolyethylene glycol (mPEG-COONSu; 2 kDa), and the properties of the resulting conjugates (mPEG-CS1, mPEG-CS2, mPEG-CS3) were investigated. The antioxidant properties of these mPEG-CSs were examined using (1) N-centered radicals derived from 1,1′-diphenyl-2-picrylhydrazyl (DPPH), (2) reducing power, based on their ability to reduce Cu2+ and (3) hydroxyl radicals via the use of ESR spectrometry. The order of their effectiveness was mPEG-CS1 > mPEG-CS2 > mPEG-CS3, i.e. mPEG-CS1 with a low particle size had the highest scavenging activity of the mPEG-CSs tested. In an in vivo study, we examined the effect of mPEG-CS1 on liver injury, caused by injecting mice with Concanavalin A (Con A). The livers of mice that were treated with mPEG-CS1 were protected from Con A-induced injury. Further, pre-treatment with mPEG-CS1 dramatically reduced the mortality associated with Con A-induced mortality. These findings suggest that mPEG-CS1 could be potentially useful in the treatment of immune-mediated liver injury.