A charge-switched nano-sized polymeric carrier for protein delivery

A novel synthetic nanocomplex was constructed from glycol chitosan (GCS) grafted with 2,3-dimethylmaleic anhydride (DMA) (denoted as ‘GCD’ hereafter) and lysozyme (isoelectric point = 10.9) as a model protein. This is a core-shell supramolecular assemble formed through electrostatic interactions between anionic GCD and cationic lysozyme at a pH 7.4. The pH-sensitivity of the nanocomplexes originates from the dissociation of DMA block from GCD at a slightly acidic pH (i.e., pH 6.8), resulting in an increased electrostatic repulsion between cationic GCS and cationic lysozyme. This pH-induced charge switching of GCD provides a mechanism for triggered protein drug release from the nanocomplexes triggered by the small change in pH (pH 7.4–6.8).