pH and Glucose Dual-Responsive Hybrid Polymeric Smart Insulin Carrier for Diabetes Treatment

Glucose-responsive smart insulin delivery systems that mimic the pancreatic insulin release system can improve the health and quality of life of patients with diabetes. In this study, a spherical drug delivery carrier encapsulating insulin was developed to achieve improved glucose accessibility and a rapid pH response using polyhedral oligomeric silsesquioxane (POSS) as a sterically stabilizing structure. Highly sensitive poly(acrylic acid) (PAA)-POSS-aminophenylboronic acid (APBA)@insulin (386 ± 69 nm), a spherical drug delivery carrier encapsulating insulin, was synthesized using POSS, a hydrophobic material, and PAA and APBA, which respond to pH and glucose, respectively. The drug carrier has dual reactivity with pH and glucose, and the synthesis of the carrier was confirmed through Fourier transform infrared (FT-IR) spectroscopy, which verified that the particles were stable at each pH through the zeta-potential data. In particular, PAA-POSS-APBA@insulin exhibited highly sensitive drug delivery characteristics, in which the backbone of PAA was expanded under acidic conditions (around pH 5.0) and insulin bound to the boronic acid inside could rapidly and selectively react with trace amounts of glucose. PAA-POSS-APBA@insulin nanoparticles exhibited no HeLa cell cytotoxicity up to a high concentration of 640 μg/mL, and the cell growth rate increased with the concentration, indicating biocompatibility. The average blood glucose level of diabetic mice treated with POSS-APBA@insulin (4.0 IU/kg) decreased for >6 h and remained stable. Thus, PAA-POSS-APBA@insulin can function as a stimulatory-responsive drug carrier targeting hyperglycemic environments.