Competitive binding-accelerated insulin release from a polypeptide nanogel for potential therapy of diabetes

Abstract

A kind of glucose-sensitive polypeptide nanogel was prepared via a two-step procedure. First, methoxy poly(ethylene glycol)-block-poly(γ-benzyl-L-glutamate-co-(γ-propargyl-L-glutamate-graft-glucose) (mPEG-b-P(BLG-co-(PLG-g-Glu))) was synthesized by clicking 2′-azidoethyl-O-α-D-glucopyranoside to the PLG unit in mPEG-b-P(BLG-co-PLG), which was synthesized by the ring-opening polymerization (ROP) of γ-benzyl-L-glutamate N-carboxyanhydride and γ-propargyl-L-glutamate N-carboxyanhydride with mPEG-NH₂ as the macroinitiator. The novel nanogel was subsequently prepared by cross-linking the glucose moieties through adipoylamidophenylboronic acid (AAPBA). The formation of the nanogel, i.e. the successful incorporation of phenylboronic acid (PBA) in the core, was systematically verified. The resultant nanogel showed a remarkable glucose-sensitivity in phosphate-buffered saline (PBS). Thus, insulin as a model drug was loaded into the glucose-sensitive polypeptide nanogel. The in vitro drug release profiles revealed that the release of insulin from the nanogel could be triggered by the presence of glucose through a competitive binding mechanism with the conjugated glucose. In detail, a faster release rate and a larger amount of released insulin were observed by the increased glucose concentration in PBS, which confirmed the potential application of the nanogel. Furthermore, the excellent cytocompatibility and hemocompatibility of the nanogel were demonstrated. Therefore, the biocompatible nanogel with an intelligent capacity for glucose-accelerated payload release should be promising for applications in diabetes treatment.