Monovalent salt enhances colloidal stability during the formation of chitosan/tripolyphosphate microgels

Chitosan micro- and nanoparticles are routinely prepared through ionotropic gelation, where sodium tripolyphosphate (TPP) is added as a cross-linker to dilute chitosan solutions. Despite the wide use of these gel-like particles, their preparation currently relies on trial and error. To address this, we used isothermal titration calorimetry (ITC), dynamic light scattering (DLS), transmission electron microscopy (TEM), and ζ-potential measurements to investigate how the formation, structure, and colloidal stability of chitosan microgels are linked to the molecular interactions that underlie their self-assembly. The strength of the chitosan/TPP interactions was systematically varied through the addition of monovalent salt (NaCl). Remarkably, and contrary to other colloidal systems, this revealed that moderate amounts of NaCl (e.g., 150 mM) enhance the colloidal stability of chitosan/TPP microgels during their formation. This stems from the weakened chitosan/TPP binding, which apparently inhibits the bridging of the newly formed microgels by TPP. The enhanced colloidal stability during the ionic cross-linking process yields microgels with dramatically narrower size distributions, which hitherto have typically required the deacetylation and fractionation of the parent chitosan. Conversely, at high ionic strengths (ca. 500 mM) the chitosan/TPP binding is weakened to the point that the microgels cease to form, thus suggesting the existence of an optimal ionic strength for ionotropic microgel preparation.