Ionically crosslinked chitosan micro- and nanogels are frequently prepared by adding tripolyphosphate (TPP) to dilute chitosan solutions. Due to their mild preparation conditions, biocompatibility and ability to protect bioactive payloads, these colloidal particles are widely explored as potential drug and gene carriers. Yet, little has been done to understand the mechanism of their ionotropic assembly. To address this, we used stopped-flow and dynamic light scattering, isothermal titration calorimetry (ITC) and electron microscopy to probe the kinetics and mechanism of chitosan/TPP microgel formation. The stopped-flow light scattering revealed that their formation rates are extremely sensitive to the monovalent salt (NaCl) and TPP concentrations, and scale roughly with [TPP]5 and [NaCl]-5. Based on these results, we used high NaCl and low TPP concentrations to dramatically slow down the microgel formation process (which typically occurs within milliseconds of mixing), so that it could be monitored over several days using conventional light scattering and electron microscopy techniques. This analysis indicated that chitosan/TPP microgel formation occurs in two stages: (1) formation of primary nanoparticles; and (2) aggregation of these nanoparticles into larger, higher-order microgels (hundreds of nanometers in diameter). Aside from reducing the microgel formation rates, the addition of NaCl enhances their colloidal stability during their preparation. This improved colloidal stability is achieved by limiting the bridging flocculation of the lyophilic microgels by TPP (which otherwise occurs during TPP addition) and results in narrower particle size distributions.

Kinetic and mechanistic analysis of chitosan/tripolyphosphate microgel formation

246th National Meeting (2013)

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