Synthesis of chitosan microgels via molybdate ionotropic gelation: a Box-Behnken design approach for efficient optimization

Chitosan microgels, generated through ionotropic crosslinking with ammonium molybdate, were synthesized through the slow dropwise addition of a dilute crosslinking solution into a dilute chitosan solution. Several variables were investigated to improve the microgel synthesis to generate small and monodisperse samples, including crosslinker to chitosan ratio, pH and addition rate. Following initial scoping work, Design-of-Experiments was implemented to reduce the z-average diameter and dispersity. Box-Behnken design successfully optimized the chitosan-ammonium molybdate microgels, resulting in sub-150 nm microgel particles with a polydispersity index below 0.200. Microgels were characterized through Dynamic Light Scanning for microgel size and dispersity, confirmed and visualized by Transmission Electron Microscopy. Overall, we developed a novel approach to prepare chitosan microgels through crosslinking with ammonium molybdate and optimized their synthesis method through Box-Behnken experimental design.