Regulated basal and bolus insulin release from glucose-responsive core-shell microspheres based on concanavalin A-sugar affinity

Individual insulin therapy considering the heterogeneity of insulin resistance between patients may bring more benefits than conventional therapy. Therefore, in glucose-responsive insulin delivery systems, more attention should be paid on further regulation of insulin release to meet individual requirements. Our study shows the feasibility of using a photo-crosslinkable shell layer to regulate basal and bolus insulin release from glucose-responsive Con A-polysaccharides network. Core-shell microspheres were fabricated through a two-step high-speed shear-emulsification method. The morphology was observed by SEM and TEM, and the core-shell structure was confirmed by the differences in chemical composition between core-shell and single-layer microspheres obtained from XPS and IR analysis. In vitro insulin release test revealed that the core-shell microspheres with or without light-irradiation could maintain corresponding bolus and basal insulin release in response to different glucose concentration but enable much lower burst release compared with single-layer microspheres without shell. Meanwhile, insulin release rate and amount could be further decreased upon light-irradiation owing to the photo-induced cycloaddition of cinnamate pendant groups of the shell material. The released insulin was proved to remain active according to fluorescence and circular dichroism analysis. The HDF cell viability assessment suggested that the core-shell microspheres possessed no in vitro cytotoxicity.