Development of shell cross-linked nanoparticles based on boronic acid-related reactions for self-regulated insulin delivery

Shell cross-linked nanoparticles were fabricated by the complexation of poly(3-methacrylamido phenylboronic acid) (PMAPBA) and thiolated chitosan (chitosan-SH) via boronic acid-related reactions. The formation of PMAPBA/chitosan-SH nanoparticles was confirmed by transmission electron microscopy, dynamic light scattering, and UV spectroscopy. The nanoparticles had a narrow size distribution with a relatively high positive charge density, and the size and zeta potential of the nanoparticles correlated with the chitosan-SH concentration. Furthermore, owing to the cross-linking of the nanoparticle shell, insulin was encapsulated in the nanoparticles with a loading capacity of up to 18%. The release of insulin from the nanoparticles slowed down because of the presence of disulfide bonds and increased with increasing glucose level in the medium. The structure of the released insulin was not distorted. More importantly, the nanoparticles had good cytocompatibility, as demonstrated by in vitro experiments. The simplicity of this strategy along with a high loading capacity, glucose sensitivity, and cytocompatibility of the produced nanoparticles should significantly boost their application in self-regulated insulin delivery.