Reactive Flash Nanoprecipitation: Expanding the Landscape of Nanoparticle Fabrication for Biomedical Applications

Scaling up nanoparticle production remains a major challenge that limits the translation of nanotechnology. Flash nanoprecipitation (FNP), first introduced by Prud'homme in 2003, offers a promising approach to bridge laboratory-scale synthesis and industrial manufacturing. Building on his pioneering studies, FNP has been applied not only to fabricate nanoparticles encapsulating hydrophobic drugs but also to generate particles with increasingly complex architectures. In this perspective, recent developments in the field are highlighted, and an emerging direction is proposed: reactive FNP (rFNP). In-situ crosslinking and possibly other chemical reactions are integrated directly into the flash nanoprecipitation process. It demonstrates that selected chemical reactions, including click chemistry and precipitation reactions, can be incorporated directly into FNP to create nanoparticles with enhanced chemical stability, improved physical properties, and broader functional capabilities. While this review is centered on new opportunities for applying rFNP-based strategies in biomedical and pharmaceutical applications, it also underscores broader possibilities for nanoparticle preparation and functionalization across a wide range of other fields.