Insulin delivery

Endocrinology

Vesicle

Hypoglycemia

Biochemistry

Hypoxia (environmental)

Insulin

Glucose oxidase

Organic chemistry

Membrane

Oxygen

Anatomy

Enzyme

Internal medicine

Type 1 diabetes

Pharmacology

Biocompatibility

Medicine

Chemistry

Hyaluronic acid

Diabetes mellitus

Proceedings of the National Academy of Sciences

Significance For exploiting synthetic glucose-responsive insulin delivery systems, challenges remain to demonstrate a strategy that would combine ( i ) fast responsiveness, ( ii ) ease of administration, and ( iii ) excellent biocompatibility. We have developed a novel glucose-responsive insulin delivery device using a painless microneedle-array patch containing hypoxia-sensitive hyaluronic acid-based vesicles. The vesicles quickly dissociate and release encapsulated insulin under the local hypoxic environment, caused by the enzymatic oxidation of glucose in the hyperglycemic state. This “smart insulin patch” with a new enzyme-based glucose-responsive mechanism can regulate the blood glucose of type 1 diabetic mice to achieve normal levels, with faster responsiveness compared with the commonly used pH-sensitive formulations, and can avoid the risk of hypoglycemia.

Microneedle-array patches loaded with hypoxia-sensitive vesicles provide fast glucose-responsive insulin delivery