Microfluidics for particle production in drug delivery: From physical basics to perspective applications

In recent years, micro- and nanoparticles have gained interest due to their applicability to diverse biomedical fields, especially drug delivery. Typical batch methods, including solvent evaporation or homogenization, achieve high production volumes but are often characterized by low reproducibility and high polydispersity. For this reason, microfluidics has recently emerged as a promising method for producing monodisperse, finely controlled, and highly tunable carriers. Depending on the material and device geometry, a wide range of particles can be obtained, spanning from the microscale to the nanoscale and from metallic to biomimetic systems. Microfluidics can reduce waste and costs because of the limited volumes employed, while enhancing throughput through parallelization. This review provides an overview of microfluidic technologies for particle production, ranging from the underlying physical principles, including dimensionless numbers, to market applications. Particular attention is devoted to the latest device geometries and materials, as well as to the implementation of artificial intelligence and emerging autonomous formulation strategies for reducing industrial costs and development times. The strengths, limitations, and potential improvements associated with each geometry and material are critically evaluated and compared to provide a comprehensive understanding of microfluidics for drug-delivery applications. Although substantial progress is still required for microfluidics to become a leading technology for industrial particle production, owing to limitations such as device clogging, chip-material compatibility, and the cost and standardization hurdles of large-scale GMP manufacturing, an increasing number of FDA-approved drug carriers may be produced through this innovative approach in the coming years.