Hari Krishnareddy Rachamala, Sreya Roy, Srujan Marepally
Lipid-based delivery systems (LDS), including lipid nanoparticles (LNPs) and liposomes, have become indispensable tools in modern biomedicine owing to their biocompatibility, capacity to encapsulate diverse therapeutic agents, and potential for targeted delivery. Despite their clinical success, conventional batch-based manufacturing methods are hindered by variability, limited scalability, and complex processing steps, slowing their broader translation. Microfluidic technologies offer a transformative solution by enabling precise fluid handling, rapid mixing, and reproducible production of LDS with tunable physicochemical attributes such as particle size, lamellarity, and drug-loading efficiency. This review highlights advances in microfluidic design strategies, including hydrodynamic flow focusing, staggered herringbone mixers, and toroidal micromixers, and evaluates how critical parameters such as flow rate, solvent composition, and lipid concentration influence LDS performance. Furthermore, we discuss the application of microfluidics in drug delivery, nucleic acid therapeutics, and vaccine platforms, underscoring its role in improving scalability, quality control, and clinical translation. Finally, we examine current challenges, including throughput limitations and solvent handling, while outlining future directions for integrating emerging materials and additive manufacturing to optimize LDS fabrication. Collectively, microfluidic platforms provide a promising pathway for next-generation lipid nanomedicines with enhanced precision, reproducibility, and therapeutic efficacy.