Advanced manufacturing of nanoparticle formulations of drugs and biologics using microfluidics

Numerous innovative nanoparticle formulations of drugs and biologics, named nano-formulations, have been developed in the last two decades. However, methods for their scaled-up production are still lagging, as the amount needed for large animal tests and clinical trials is typically orders of magnitude larger. This manufacturing challenge poses a critical barrier to successfully translating various nano-formulations. This review focuses on how microfluidics technology has become a powerful tool to overcome this challenge by synthesizing various nano-formulations with improved particle properties and product purity in large quantities. This microfluidic-based manufacturing is enabled by microfluidic mixing, which is capable of the precise and continuous control of the synthesis of nano-formulations. We further discuss the specific applications of hydrodynamic flow focusing, a staggered herringbone micromixer, a T-junction mixer, a micro-droplet generator, and a glass capillary on various types of nano-formulations of polymeric, lipid, inorganic, and nanocrystals. Various separation and purification microfluidic methods to enhance the product purity are reviewed, including acoustofluidics, hydrodynamics, and dielectrophoresis. We further discuss the challenges of microfluidics being used by broader research and industrial communities. We also provide future outlooks of its enormous potential as a decentralized approach for manufacturing nano-formulations.