(40d) Standing on the Shoulders of Flash Nanoprecipitation: Sequential Nanoprecipitation for the Continuous Manufacturing of Nanoparticles and Microparticles

Sequential NanoPrecipitation (SNaP) is a nascent controlled precipitation process for the tunable formation of polymeric particles for drug delivery and bioimaging. While SNaP relies on the same self-assembly principles as one-step Flash NanoPrecipitation, SNaP is a two-step assembly process in which the particle core assembly is initiated during a first mixing step followed by particle stabilization in a second mixing step. Decoupling the particle assembly steps improves control over the particle structure and expands the attainable particle size range to include microparticles. Using a novel sequential mixer design, we attain unprecedented control over a key process variable: the delay time between the formation of the particle core and the particle stabilization. We demonstrate that particle size scales with delay time in agreement with Smoluchowski’s model of diffusion-limited particle growth. This enables us to synthesize particles ranging from 50 nm to 5 µm in diameter and to encapsulate small molecule active pharmaceutical ingredients (APIs) and fluorophores with high encapsulation efficiencies via SNaP. Furthermore, SNaP can uniformly assemble components with different assembly timescales, for example, inorganic nanocrystals, polymer coils and small molecules, by affording control over the order of component addition and the delay time between additions. The novel SNaP process will unlock new particle architectures and open new avenues for nanoparticle and microparticle manufacturing in industry.

In honor of Prof. Bob Prud’homme’s illustrious and impactful career as a curious scientist, engineer and mentor.