Facile one-pot synthesis of glucose-sensitive nanogel via thiol-ene click chemistry for self-regulated drug delivery

A novel glucose-sensitive nanogel was conveniently prepared through one-pot thiol-ene copolymerization of pentaerythritol tetra(3-mercaptopropionate), poly(ethylene glycol) diacrylate, methoxyl poly(ethylene glycol) acrylate and N-acryloyl-3-aminophenylboronic acid. The formation of core–shell nanogel was verified by proton nuclear magnetic resonance, dynamic laser scattering (DLS) and transmission electron microscopy. The successful incorporation of phenylboronic acid (PBA) in the nanogel was confirmed through Fourier transform infrared spectroscopy, inductively coupled plasma mass spectrometry and fluorescence technology. Owing to the presence of PBA, the nanogel exhibited high glucose sensitivity in phosphate-buffered saline determined by DLS and fluorescence technology. The increased amount of glucose causes an increase in the hydrodrodynamic radius and a decrease in the fluorescence intensity of PBA–alizarin red S (ARS) complex in the nanogel at pH 7.4 because of the competitive substitution of ARS to form the hydrophilic PBA–glucose complex. ARS and insulin were loaded into this glucose-sensitive nanogel. In vitro release profiles revealed that the drug release from the nanogel could be triggered by the presence of glucose. The more glucose in the release medium, the more drug was released and the faster the release rate. Furthermore, in vitro methyl thiazolyl tetrazolium assay, lactate dehydrogenase assay and hemolysis test suggested that the nanogel was biocompatible. Therefore, the PBA-incorporated nanogel with high glucose-sensitivity and good biocompatibility may have great potential for self-regulated drug release.