Research Paper

Journal of Nanoparticle Research

, Volume 13, Issue 9, pp 4109-4120

First online:

Self-assembling process of flash nanoprecipitation in a multi-inlet vortex mixer to produce drug-loaded polymeric nanoparticles

  • Hao ShenAffiliated withDepartment of Chemical Engineering, University of Illinois at Chicago
  • , Seungpyo HongAffiliated withDepartment of Biopharmaceutical Sciences, University of Illinois at Chicago
  • , Robert K. Prud’hommeAffiliated withDepartment of Chemical Engineering, Princeton University
  • , Ying LiuAffiliated withDepartment of Chemical Engineering, University of Illinois at ChicagoDepartment of Biopharmaceutical Sciences, University of Illinois at Chicago Email author 

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We present an experimental study of self-assembled polymeric nanoparticles in the process of flash nanoprecipitation using a multi-inlet vortex mixer (MIVM). β-Carotene and polyethyleneimine (PEI) are used as a model drug and a macromolecule, respectively, and encapsulated in diblock copolymers. Flow patterns in the MIVM are microscopically visualized by mixing iron nitrate (Fe(NO3)3) and potassium thiocyanate (KSCN) to precipitate Fe(SCN) x (3−x)+ . Effects of physical parameters, including Reynolds number, supersaturation rate, interaction force, and drug-loading rate, on size distribution of the nanoparticle suspensions are investigated. It is critical for the nanoprecipitation process to have a short mixing time, so that the solvent replacement starts homogeneously in the reactor. The properties of the nanoparticles depend on the competitive kinetics of polymer aggregation and organic solute nucleation and growth. We report the existence of a threshold Reynolds number over which nanoparticle sizes become independent of mixing. A similar value of the threshold Reynolds number is confirmed by independent measurements of particle size, flow-pattern visualization, and our previous numerical simulation along with experimental study of competitive reactions in the MIVM.


Reynolds number Supersaturation Competitive kinetics Nucleation and growth Micellization Micromixing Synthesis Colloids