Human-relevant preclinical platforms for malaria: converging nanomedicine and organ-on-chip technologies

Progress in malaria control has stalled, as drug-resistant parasites and insecticide-resistant vectors erode established interventions. In parallel, nanomedicine and organ-on-chip (OoC) technologies have matured as complementary platforms with distinct strengths: the former can sharpen the targeting, efficacy, and safety of antimalarial agents, whereas the latter can reconstruct aspects of human tissue physiology that conventional animal models do not capture. This review argues that their convergence- assessing antimalarial nanomedicines within human malaria-on-chip systems, offers a preclinical layer whose value is best defined by explicit contexts of use rather than by generic promise. It surveys recent progress in lipid-, polymeric-, inorganic-, and plant-derived nanoparticles drug delivery, vaccination, and diagnostics, and connects these advances to spleen-on-chip and multi-organ malaria-on-chip models that reproduce key features of Plasmodium blood-stage biology under flow. It then specifies how integrated systems could change preclinical decisions by exposing mononuclear phagocyte clearance, shear-dependent targeting, organ-specific toxicity, immune interactions, and cryptic splenic and bone marrow reservoirs in Plasmodium vivax infection, while remaining candid about throughput, manufacturing, cost, and equity constraints in endemic settings. Finally, it frames the standardization, biological fidelity, and regulatory conditions, including a realistic reading of the FDA Modernization Act 2.0, that must be met before nano–organ–on–chip systems can serve as reliable, decision-enabling tools for antimalarial development.