Non-stoichiometric Coacervation between Hyaluronic Acid and Chitosan

Hyaluronic acid and chitosan present a unique non-cognate pair where both polyelectrolytes are semi-flexible and have pH-dependent charges. These oppositely charged polysaccharides go into liquid-liquid phase separation far away from zero-zeta potential, which usually takes place at 1:1 charge ratios for other oppositely charged macroion-pairs. In this presentation, we explore the reasons behind non-stoichiometric coacervation for the HA/CHI pair. We also briefly studied effect of counterions on the coacervation window; i.e. extend of charge ratios where coacervation prevailed. If the counterion was present as a small ion of the solvent solution (Na⁺ or Ca⁺²), then its chaotropic nature had an effect of keeping the polymer hydrated despite the tendency to release the water molecules upon association of the polymers. This effect was enhanced when the polyelectrolyte had glutamate instead of chloride as its counterion. Since glutamate was a large zwitterion where the charge was distributed around different atoms, it served to extend the coacervation window.