Microfluidic reactors for the synthesis of inorganic and hybrid nanoparticles for drug delivery

Inorganic nanoparticles (NPs) have played a central role in the development of nanomedicine, offering unique physicochemical properties that enable imaging, therapy, and multifunctional drug delivery. Despite extensive progress, the clinical translation of nanomedicines remains limited, largely due to challenges associated with reproducibility, scalability, toxicity, and, critically, inefficient delivery to target tissues. In this context, microfluidic technologies have emerged as a powerful platform to address many of these limitations by enabling continuous, highly controlled, and reproducible NP synthesis under well-defined flow conditions. This review provides a comprehensive overview of recent advances in the continuous-flow microfluidic synthesis of inorganic NPs for drug delivery applications. Key microfluidic parameters governing NP formation are discussed, including mixing regimes, residence time, flow configuration, and scale-up, and analyze how these factors influence size, dispersity, composition, and functional performance. Particular attention is devoted to plasmonic NPs, non-metallic magnetic NPs, and other relevant inorganic systems such as quantum dots and silica NPs, highlighting both achievements and remaining challenges in their microfluidic production. Beyond purely inorganic NPs, the review examines the growing field of hybrid organic-inorganic NPs, where inorganic cores are integrated with polymers, lipids, or biomimetic components to combine synthetic functionality with biological performance. These hybrid architectures represent a promising strategy to overcome key barriers in drug delivery, including immune clearance, poor targeting efficiency, and limited therapeutic index, while posing additional synthetic and integration challenges that microfluidics is uniquely positioned to address. Finally, current bottlenecks and future perspectives for microfluidic nanomanufacturing are discussed, including productivity, multistep process integration, in-line purification, and automation. Microfluidic platforms, especially when combined with hybrid and bioinspired NP design, are positioned as enabling technologies to bridge the gap between advanced NP engineering and clinically translatable nanomedicines.