Smart erythrocyte-hitchhiking insulin delivery system for prolonged automatic blood glucose control

Long and automatic control of blood glucose levels in diabetic patients could solve the problems caused by frequent insulin injections. Herein, we exploited the protection potential of erythrocytes by a "hitchhiking" strategy to significantly prolong the blood circulation time of a specifically-designed smart hitchhiking insulin delivery system (SHIDS). In the SHIDS, insulin, glucose oxidase, and catalase were co-loaded into nanoparticles formed by modified chitosan. The free glucosamines in chitosan anchor glucose transporters on the surface of erythrocytes, allowing erythrocyte-hitchhiking in the blood flow. A high glucose level triggers quick insulin release from the SHIDS to reduce the glucose level, which then slows the insulin release. This closed-loop glucose regulation by the SHIDS effectively controlled blood glucose within the normal range for at least 24 h and under 250 mg dL^-1 for ∼48 h with one injection. This injectable erythrocyte-hitchhiking nanoplatform, which achieves long-term and automatic blood glucose control, thus has potential for further development. As the carrier could be used for delivering other drugs/agents or interacting with other substances, the hitchhiking strategy is versatile and may be applied in other medical applications too.