Development of glucose oxidase-immobilized alginate nanoparticles for enhanced glucose-triggered insulin delivery in diabetic mice

In this work, we successfully developed poly(acrylamido phenylboronic acid)/sodium alginate nanoparticles (NPs) via formation of cycloborates (glucose- and H2O2-responsive functional groups), as an improved glucose-mediated insulin delivery system loaded with glucose oxidase (GOx). Dynamic light scattering revealed that the GOx-loaded NPs showed better glucose-sensitivity than the GOx-unloaded NPs. In addition, compared to insulin-loaded NPs, the insulin/GOx-loaded NPs displayed faster glucose-responsive insulin release. Importantly, there was a significant hypoglycemic effect on diabetic mice following the subcutaneous injection of insulin/GOx-loaded NPs. Furthermore, the NPs exhibited favorable biocompatibility as demonstrated by cytotoxicity assay, hemolysis study, and histopathological examination. The NPs have the advantages of easy preparation, enhanced glucose-responsiveness, and good biocompatibility, making them as potential candidates for subcutaneous insu-lin delivery. (C) 2020 Elsevier B.V. All rights reserved.