CFD approaches in microfluidics for the development of polymeric, lipid-based and inorganic nanoparticles for drug delivery

Microfluidics is an innovative approach for manufacturing nanoparticles in a precise and controllable manner. However, the experimental optimization of microfluidic nanoparticle fabrication faces challenges related to the intricate interplay of various process parameters within the microscale environment. The integration of experiments and computational fluid dynamics (CFD) offers a synergistic approach that allows the researchers to validate and optimize theoretical models with real-world experimental models, enhancing the precision of nanoparticle synthesis and facilitating the design of more efficient microfluidic systems. This review provides a critical analysis of the current state of knowledge on recent advances of numerical investigations for nanoparticle synthesis using microfluidic-based methods. In particular, an overview of CFD assisted studies for microfluidic production of nanoparticles is presented, whilst their advantages and limitations are discussed. The importance of numerical modelling using CFD on the understanding of droplet generation, mixing and reaction mechanisms and how these phenomena are associated with nanoparticle nucleation and growth are highlighted. Different microfluidic-based approaches to produce uniform nanoparticles are presented and the most promising techniques are identified and discussed in detail. Both passive and active mixing microfluidic strategies are considered, highlighting their impact on nanoparticle formation. A comparative study of experimental and numerical approaches is performed to provide a better understanding of the droplet breakup mechanisms and the influence of physicochemical parameters on the size and shape of the produced nanoparticles. The review confirms that adoption of CFD simulations can be beneficial to identify critical flow conditions and reaction zones, which are essential for controlling the synthesis of nanoparticles. Finally, by systematically integrating CFD with experimentation, it will be possible to translate microfluidic nanoparticle synthesis into scalable and industrially viable technologies.