Glucose‐Responsive Modified Poly(Propylene Imine) Dendrimer for Self‐Regulated Insulin Delivery

Diabetes is characterized by inadequate insulin secretion and elevated blood glucose levels, and patients require continuous insulin infusion and continuous glucose monitoring. Self‐regulating insulin delivery systems, which use glucose‐sensitive materials for dynamic and automatic insulin release, have been considered as a solution to alleviate these problems. In this study, poly(propylene imine) dendrimers functionalized with phenolboronic acid (PBA) are synthesized and modified to develop a glucose‐sensitive system with a suitable p K a under physiological conditions. The results showed that the p K a of PBA decreased from ∼8 to 7.35 after attachment to the dendrimer due to the effect of the amino groups and increased acidity. Also, the equilibrium binding constant ( K eq‐tet ) for PBA‐attached G4 dendrimer (HB‐CBA) was determined to be 79 m −1 by the spectral method. Dynamic light scattering (DLS) analysis confirmed the sensitivity of the system to glucose; the particle size of HB‐CBA at pH 7.5 increased from 179 nm without glucose to 192 and 246 nm in the presence of 1 and 3 mg/mL glucose. The encapsulation efficiency (EE) and loading capacity (LC) were 92% and 2.3%, respectively. Insulin release was observed in a glucose‐dependent manner: about 82% at 3 mg/mL, about 48% at 1 mg/mL, and 26% in glucose‐free medium. These results indicate that HB‐CBA is a smart and glucose‐sensitive carrier that can regulate insulin release based on the glucose level and provide effective performance in self‐regulating drug delivery.