Human Multi-Organ-on-a-Chip Platforms for Next-Generation Drug Delivery Strategies

Human multi-organ-on-a-chip (MOoC) platforms have rapidly emerged as next-generation preclinical models for evaluating therapeutic delivery and efficacy. By integrating dynamic perfusion, physiologically relevant microenvironments, and systemic tissue-tissue crosstalk, MOoCs provide unprecedented opportunities to study drug absorption, distribution, metabolism, and toxicity under human-relevant conditions. In this review, we summarize recent progress in MOoC technologies and their application to diverse drug delivery strategies, including stem cell-based carriers, gene and nucleic acid therapies, nanoparticles, extracellular vesicles, and biomaterials. We highlight how these systems overcome key limitations of conventional in vitro and animal models, offering more predictive insight into therapeutic distribution and pharmacodynamics. Key technical and biological considerations, including material limitations, physiological scaling, and incorporation of patient-specific components, are discussed in the context of ongoing engineering developments. These platforms enable assessment of organ-specific accumulation, metabolic transformation, and off-target effects that are poorly captured by traditional methods. Finally, we outline future perspectives for MOoCs as translational platforms poised to accelerate drug discovery, reduce clinical attrition, and support the development of precision medicines.