Control and Preparation of Quaternized Chitosan and Carboxymethyl Chitosan Nanoscale Polyelectrolyte Complexes Based on Reactive Flash Nanoprecipitation

[Image: see text] Nanoscale polyelectrolyte complex materials have been extensively investigated for their promising application in protocell, drug carriers, imaging, and catalysis. However, the conventional preparation approach involving positive and negative polyelectrolytes leads to large size, wide size distribution, instability, and aggregation due to the nonhomogeneous mixing process. Herein, we employ reactive flash nanoprecipitation (RFNP) to control the mixing and preparation of the nanoscale polyelectrolyte complex. With RFNP, homogeneous mixing complexation between oppositely charged chitosan derivatives could be achieved, resulting in stable nanoscale complexes (NCs) with controllable size and narrow size distribution. The smallest size of NCs is found at specific pH due to the maximum attraction of positive and negative molecules of chitosan. The size can be modulated by altering the volumetric flow rates of inlet streams, concentration, and charge molar ratio of two oppositely charged chitosan derivatives. The charge molar ratio is also tuned to create NCs with positive and negative shells. There is no significant variation in the size of NCs produced at different intervals of time. This method allows continuous and tunable NC production and could have the potential for fast, practical translation.