The pH-Responsive CS-g-PEI-g-PEG Graft Copolymer as PolyI:C/OVA Drug Carrier

The chitosan-g-polyethyleneimine-g-polyethylene glycol graft copolymer was synthesized for delivery of the immunomodulatory agent polyinosinic-polycytidylic acid and the mimetic antigen ovalbumin. The ¹H-NMR results showed that polyethylene glycol was successfully grafted onto chitosan-g-polyethyleneimine copolymer by Schiff base reaction in a normal physiological environment (pH 7.4), while polyethylene glycol segments were detached from copolymer in a slightly acidic environment (pH 5.0). The results of cytotoxicity showed that graft copolymer with the modification degree of 47% had very low cytotoxicity, and the cell survival rate was above 95%. Nanoparticles of chitosan-g-polyethyleneimine-g-polyethylene glycol graft copolymer and polyinosinic-polycytidylic acid with different negative/positive charge ratios were obtained by electrostatic self-assembly between graft copolymer, polyinosinic-polycytidylic acid, and ovalbumin. The agarose gel electrophoresis results showed that polyinosinic-polycytidylic acid was well coated by the graft copolymer and protected from nuclease degradation. The performance study of nanoparticles results showed that their particle size with the negative/positive charge ratio of 40 : 1 was about 58 nm, which had the best solution stability, and the encapsulation efficiency of ovalbumin was ~50%, and it also significantly promoted the secretion of TNF-α and IFN-γ.