Effects of histidine modification of chitosan microparticles on metal ion adsorption

Imbalances in metal ions (Cu2+, Fe3+, and Zn2+) augment oxidative stress, and can lead to amyloid-beta (A beta) peptide aggregation, a phenomenon that is associated with Alzheimer's disease (AD) progression. As such, the use of particles that can cross the blood-brain barrier (BBB) and chelate metals could potentially provide a therapy to restore ionic balance in AD. Herein, we functionalized chitosan microparticles (CM) with histidine (an amino acid that contains an imidazole group, therefore mimicking A beta) to chelate Cu2+, Fe3+, and Zn2+. CM were prepared by spray-drying and and functionalized with histidine (CM-Histidine). The CM, before and after functionalization, and interacting with metal ions were characterized by scanning electron microscopy with energy dispersive spectroscopy, x-ray diffraction and potentiometric titration. The adsorption capacity of CM-Histidine increased for Cu2+ and decreased for Zn2+ and Fe3+, when compared to unmodified CM. However, the adsorption kinetics for Cu2+ ions was lower for CM-histidine, than for CM, and the reverse was observed for Zn2+ and Fe3+. External mass resistance was the major factor that defined the mass transfer mechanism onto the active sites of CM-histidine. Diffusional effects were more relevant for Zn(2+ )and Fe3+ in the sorption process than for Cu2+.