Design of genipin-crosslinked microgels from concanavalin A and glucosyloxyethyl acrylated chitosan for glucose-responsive insulin delivery

Glucose-responsive systems are significant for self-regulated insulin delivery. The aim of this study was to assess the potential of genipin-crosslinked concanavalin A/GEA-chitosan microgels as a glucose-responsive insulin delivery system. A chitosan derivative (GEA-chitosan) was designed in this study as the polymer ligand of concanavalin A (Con A), which not only exhibits a strong affinity to Con A, but also could be directly crosslinked with Con A by genipin, thus avoiding the modification of Con A during an immobilization process. Glucose responsive microgels were fabricated by the reversed-phase emulsion crosslinking method. The in vitro release of insulin indicated that the insulin release was influenced by glucose concentrations, and a desired pulsatile release behavior was detected in response to stepwise glucose challenges for more than eight cycles. The release data were fitted well to an exponential model, without any significant influence of the surface effect. The released insulin was proved to remain active without destruction of the tertiary structure. The analysis of L929 cells viability suggested that these microgels possessed no in vitro cytotoxicity. The obtained genipin crosslinked Con A/GEA-chitosan microgels might be a potential candidate for self-regulated insulin delivery.