Fabrication of Biobased Polyelectrolyte Capsules and Their Application for Glucose-Triggered Insulin Delivery.

To enhance the glucose sensitivity and self-regulated release of insulin, biobased capsules with glucose-responsive and competitive properties were fabricated based on poly(γ-glutamic acid) (γ-PGA) and chitosan oligosaccharide (CS) polyelectrolytes. First, poly(γ-glutamic acid)-g-3-aminophenylboronic acid) (γ-PGA-g-APBA) and galactosylated chitosan oligosaccharide (GC) were synthesized by grafting APBA and lactobionic acid (LA) to γ-PGA and CS, respectively. The (γ-PGA-g-APBA/GC)5 capsules were then prepared by layer-by-layer (LBL) assembly of γ-PGA-g-APBA and GC via electrostatic interaction. The size and morphology of the particles and capsules were investigated by DLS, SEM, and TEM. The size of the (γ-PGA-g-APBA/GC)5 capsules increased with increasing glucose concentration due to the swelling of the capsules. The capsules could be dissociated at high glucose concentration due to the breaking of the cross-linking bonds between APBA and LA by the competitive reaction of APBA with glucose. The encapsulated insulin was able to undergo self-regulated release from the capsules depending on the glucose level and APBA composition. The amount of insulin release increased with incubation in higher glucose concentration and decreased with higher APBA composition. Moreover, the on-off regulation of insulin release from the (γ-PGA-g-APBA/GC)5 capsules could be triggered with a synchronizing and variation of the external glucose concentration, whereas the capsules without the LA functional groups did not show the on-off regulated release. Furthermore, the (γ-PGA-g-APBA/GC)5 capsules are biocompatible. These (γ-PGA-g-APBA/GC)5 with good stability, glucose response, and controlled insulin delivery are expected to be used for future applications to glucose-triggered insulin delivery.