pH-sensitive peptide hydrogel for glucose-responsive insulin delivery

Publication date: Available online 6 January 2017
Source:Acta Biomaterialia
Author(s): Xue Li, Mian Fu, Jun Wu, Chenyu Zhang, Xin Deng, Arvind Dhinakar, Wenlong Huang, Hai Qian, Liang Ge
Glucose-responsive system is one of important options for self-regulated insulin delivery to treat diabetes, which has become an issue of great public health concern in the world. In this study, we developed a novel and biocompatible glucose-responsive insulin delivery system using a pH-sensitive peptide hydrogel as a carrier loaded with glucose oxidase, catalase and insulin. The peptide could self-assemble into hydrogel under physiological conditions. When hypoglycemia is encountered, neighboring alkaline amino acid side chains are significantly repulsed due to reduced local pH by the enzymatic conversion of glucose into glucoinc acid. This is followed by unfolding of individual hairpins, disassembly and release of insulin. The glucose-responsive hydrogel system was characterized on the basis of structure, conformation, rheology, morphology, acid-sensitivity and the amount of consistent release of insulin in vitro and vivo. The results illustrated that our system can not only regulate the blood glucose levels in vitro but also in mice models having STZ-induced diabetes.Statement of SignificanceIn this report, we have shown the following significance supported by the experimental results.1, we successfully developed, characterized and screened a novel pH-responsive peptide2, we successfully developed a novel and biocompatible pH-sensitive peptide hydrogel as glucose-responsive insulin delivery system loaded with glucose oxidase, catalase and insulin.3, we successfully confirmed that the hydrogel platform could regulate the blood glucose level in vitro and in vivo.Overall, we have shown enough significance and novelty with this smart hydrogel platform in terms of biomaterials, peptide chemistry, self-assembly, hydrogel and drug delivery. So we believe this manuscript is suitable for Acta Biomaterialia.

Graphical abstract

http://ift.tt/2j1AwRB