Effects of quaternization and PEGylation on the biocompatibility, enzymatic degradability and antioxidant activity of chitosan derivatives

Chitosan-N-trimethylaminoethylmethacrylate chloride (CS-TM) copolymers with different quaternization degrees (DQ, 30 and 50%) were synthesized and further modified with methoxypoly(ethylene glycol) (mPEG) of different molecular weights (MW, 2 and 5 kDa). The hydrophilicity of the resulting copolymers was significantly increased as evidenced by decreased contact angles. PEGylation with higher mPEG MW could significantly reduce the hemolytic potential, protein adsorption, cytotoxicity and intestinal mucosal damage of CS-TM (DQ of 50%, CS-TM50). PEGylation resulted in a considerable increase in the release of reducing sugars following 84-day lysozyme-catalyzed degradation, and an increase in mPEG MW led to a faster degradation of CS-TM50. The antioxidant activity of CS-TM50 was superior to that of PEGylated CS-TM50, exhibiting dose-dependent reducing power and lipid peroxidation inhibition effect. In conclusion, quaternization and subsequent PEGylation of CS with rational modification degree of its free amino group will be a potential strategy for the development of biocompatible and biodegradable CS derivatives.