Monovalent Salt-Controlled Assembly of Chitosan/Tripolyphosphate Microgels

Self-assembled chitosan/tripolyphosphate (TPP) microgels have attracted interest in a wide range of applications (e.g., drug/gene delivery and foods), which require control over their size distributions. This control is typically achieved by modifying the chitosan structure (i.e., molecular weight and degree of deacetylation) and solute compositions used during microgel preparation. These methods, however, are based on trial and error, and provide little mechanistic insight on the phenomena that underlie this structural control. To address this, we used isothermal titration calorimetry (ITC), dynamic and electrophoretic light scattering, transmission electron microscopy (TEM), and stopped-flow turbidimetry to relate the molecular chitosan/TPP interactions to microgel formation, structure and colloidal stability. This revealed that the addition of moderate amounts of monovalent salt (e.g., 150 mM NaCl) can inhibit microgel coagulation during their formation process. This enhancement in colloidal stability yields microgels with much lower polydispersities than those achieved in the absence of monovalent salt. Conversely, when the ionic strength is increased further, the chitosan/TPP binding is weakened to the point that the microgels cease to form. This suggests that the formation and ultimate size distributions of ionically-crosslinked microgels depend on the polymer/crosslinker binding strength, and can be controlled by varying the monovalent salt concentration used during their formation.