Microfluidic engineering of polymer-based drug delivery systems: From particle synthesis to organ-on-a-chip...

The convergence of microfluidic engineering and organ-on-a-chip (OoC) technology is redefining the development and preclinical validation of polymer-based drug delivery systems and biomedical preparations. This review presents a bidirectional framework: first, how microfluidics enables precision synthesis of polymer particles with controlled size, morphology and multifunctionality; second, how OoC platforms serve as physiologically relevant testbeds to evaluate these particles under dynamic, human-mimetic conditions. We examine droplet microfluidics principles for generating monodisperse polymer particles (spheres, Janus, core-shell, porous architectures) from natural and synthetic polymers. These particles are explored as functional additives within OoC systems, as embedded sensors for real-time oxygen/pH monitoring, as controlled-release depots for localized growth factor delivery and as building blocks (microscaffolds, bioinks, spheroid templates) for constructing three-dimensional tissue microenvironments. Conversely, we critically analyze how OoC platforms, including vascularized tumor models, liver-kidney multi-organ chips and blood-brain barrier systems, enable more physiologically relevant assessment of micro- and nanoparticle transport, extravasation, toxicity, immunogenicity and metabolism under fluidic shear and multi-cellular complexity, which are capabilities inaccessible to static cultures. Current challenges (scalability, GMP compliance, standardization, regulatory context-of-use) and emerging opportunities (smart responsive particles, personalized screening using patient-derived organoids, AI-driven automation and closed-loop optimization) are critically discussed. This review demonstrates that microfluidic particle engineering and OoC technology together form an iterative framework for advancing next-generation biomaterials and supporting their preclinical-to-clinical development pathway.