Glucose and pH Dual-Responsive Nanogels for Efficient Protein Delivery

Direct delivery of protein suffers from their in vitro and in vivo instability, immunogenicity, and a relatively short half-life within the body. To overcome these challenges, pH and glucose dual-responsive biodegradable nanogels comprised of dextran and poly(L-glutamic acid)-g-methoxy poly-(ethylene glycol)/phenyl boronic acid (PLG-g-mPEG/PBA) are designed. The cross-linked network imparted drug-loading efficacy of α-amylase up to 55.6% and hyaluronidase up to 29.1%. In vitro protein release profiles reveal that the release of protein is highly dependent on the pH or glucose concentrations, that is, less amount of protein is released at pH 7.4 or healthy blood glucose level (1 mg mL^-1 glucose), while quicker release of protein occurs at pH 5.5 or diabetic blood glucose level (above 3 mg mL^-1 glucose). Circular dichroism spectra show that the secondary structure of released protein is maintained compared to naive protein. Overall, the nanogels have provided a simple and effective strategy to deliver protein.