Glucose-responsive complex micelles for self-regulated release of insulin under physiological conditions

Phenylboronic acid (PBA)-based polymers have attracted much attention because of their potential applications in glucose-responsive insulin delivery for the treatment of diabetes. Herein, we prepared a kind of glucose-responsive complex micelles by the complexation between a phenylboronic acid-containing block copolymer PEG-b-P(Asp-co-AspPBA) and a glycopolymer P(Asp-co-AGA). The complex micelles combined a variety of advantages such as stability against aggregation due to the PEG shell, fast response to glucose at neutral pH due to the complex core composed of two hydrophilic polymers, and more importantly better glucose sensitivity ascribed to the decreased apparent pK(a) of the PBA/AGA complex. Moreover, glucose-triggered on-off release of insulin was obtained under physiological pH 7.4 with 2 g L-1 glucose (hyperglycemia), which provided us with an effective strategy for self-regulated insulin delivery in response to physiological glucose level. The enhanced biocompatibility of this complex micelles system was confirmed by MTT assay. This type of complex micelles may be a promising candidate for in vivo insulin delivery.