Novel Glucose-Responsive Insulin Formulations Using Chemically Modified Insulin Derivatives and Non-Covalent Insulin-Binding Molecules

Compounds, compositions, and methods for “smart” delivery of a therapeutic, prophylactic or diagnostic agent, such as glucose-mediated delivery of insulin through glucose-sensing insulin derivatives, are provided. The insulin derivatives bind serum albumin or agglomerate in vivo. The insulin derivatives effectively dissociate to release insulin in a hyperglycemic condition, where the complexation of glucose to a glucose-sensing element alters properties of the insulin derivative leading to the dissociation. The compounds, compositions, and methods provide a delivery strategy for both self-regulated and long-term diabetes management.