Hydrothermally treated chitosan spontaneously forms water-soluble spherical particles stable at a wide pH range

The authors report the spontaneous formation of water-soluble chitosan-tartaric acid (CS-TA) spherical particles. Particles are formed by heating chitosan in the presence of tartaric acid under hydrothermal conditions. Tartaric acid serves as an ionic cross-linker, a depolymerizing agent, and a particle stabilizer in aqueous phase. The CS-TA particles exhibit superior colloidal stability at a wide pH range due to their surface charge tunability, which is due to the colocalization of surface hydroxyl, amine, and carboxyl groups. At physiological pH condition, particles have zwitterionic structure as determined by the zeta potential measurements. Still, CS-TA maintains colloidal stability at neutral pH due to the abundance of surface hydroxyl groups. As a proof-of-concept study, the CS-TA particles were labeled with a model insoluble cargo (fluorescein isothiocyanate [FITC]) to demonstrate their capacity for solubilizing hydrophobic drugs. The CS-TA/FITC conjugates were found to remain well dispersed at neutral pH, while maintaining FITC fluorescence properties.