Glucose-Sensitive Polyphosphoester Diblock Copolymer for an Insulin Delivery System.

In this study, we report a diblock copolymer based on a polyphosphate backbone and pendant phenylboronic acid with glucose sensitivity. The copolymer, abbreviated as (PBYP-g-MPBA)-b-PEEP, was prepared via a combination of ring-opening copolymerization, "click" chemistry, and amide reaction, in which the PBYP and PEEP blocks, respectively, represent two kinds of polyphosphoester structures and MPBA represents 3-mercaptopropionic acid modified with 3-aminophenylboronic acid. The amphiphilic copolymer (PBYP-g-MPBA)-b-PEEP could self-assemble into core-shell nanoparticles (NPs) in aqueous solutions. The average particle size and morphology of the NPs were measured by dynamic light scattering and transmission electron microscopy, respectively. The phenomenon that the NPs swelled at different glucose concentrations is due to the formation of boronate esters between the diol groups of glucose and boronic acid groups of phenylboronic acid. Fluorescein isothiocyanate (FITC)-insulin was loaded into the NPs and triggered to release in the presence of glucose. The more the glucose in the release media, the more the FITC-insulin released and the faster the release rate. Methyl thiazolyl tetrazolium assays and hemolysis tests proved that the (PBYP-g-MPBA)-b-PEEP copolymers had good biocompatibility. All of these results verify that the glucose-sensitive polyphosphoester diblock copolymer is highly promising for an insulin delivery system.