Flash nanocomplexation (FNC): A new microvolume mixing method for nanomedicine formulation

The application of nanotechnologies in formulation has significantly promoted the development of modern medical and pharmacological science, especially for nanoparticle-based drug delivery, bioimaging, and theranostics. The advancement of engineering particle design and fabrication is largely supported by a better understanding of how their apparent characteristics (e.g., size and size distribution, surface morphology, colloidal stability, chemical composition) influence their in vivo biological performance, which raises an urgent need for practical nanoformulation methods. Based on turbulent flow mixing and the self-assembly of molecules in fluids, flash technologies emerged as effective bottom-up fabrication strategies for effective nanoformulation. Among the flash technology family, flash nanocomplexation (FNC) is considered a novel and promising candidate that can promote and optimize formulation processes in a precise spatiotemporal manner, thus obtaining excellent fabrication efficiency, reproducibility and expandability. This review presents an overview of recent advances in fabricating drug-delivery nanoparticles using FNC platforms. Firstly, brief introductions to the basic principles of FNC technology were carried out, followed by descriptions of turbulent microvolume mixers that have significantly promoted the efficiency of FNC-based fabrications. Applications of real formulation cases were then categorized according to the self-assembly-driven interactions (including electrostatic interaction, coordination interaction, hydrogen bonding and hydrophobic interaction) and discussed to reveal the progressiveness of fabricating nanoparticles and discuss how its flexibility will provide advances and replenish the philosophy of nanomedicine formulation. In the end, the commercial potential, current limitations, and prospects of FNC technology for nanoformulation will be summarized and discussed.