An Engineered Nanosugar Enables Rapid and Sustained Glucose-Responsive Insulin Delivery in Diabetic Mice

Glucose-responsive insulin-delivery platforms that are sensitive to dynamic
glucose concentration fluctuations and provide both rapid and prolonged
insulin release have great potential to control hyperglycemia and avoid hypoglycemia
diabetes. Here, biodegradable and charge-switchable phytoglycogen
nanoparticles capable of glucose-stimulated insulin release are engineered.
The nanoparticles are “nanosugars” bearing glucose-sensitive phenylboronic
acid groups and amine moieties that allow effective complexation with insulin
(≈95% loading capacity) to form nanocomplexes. A single subcutaneous
injection of nanocomplexes shows a rapid and efficient response to a glucose
challenge in two distinct diabetic mouse models, resulting in optimal blood
glucose levels (below 200 mg dL–1) for up to 13 h. The morphology of the
nanocomplexes is found to be key to controlling rapid and extended glucoseregulated
insulin delivery in vivo. These studies reveal that the injected
nanocomplexes enabled efficient insulin release in the mouse, with optimal
bioavailability, pharmacokinetics, and safety profiles. These results highlight
a promising strategy for the development of a glucose-responsive insulin
delivery system based on a natural and biodegradable nanosugar.