From Physicochemical Promise to Translational Readiness: An Evidence Map of Nano- and Targeted Drug Delivery Systems

Nano- and targeted drug-delivery systems are frequently evaluated through favorable physicochemical attributes, mechanistic plausibility, or localized preclinical performance, although these forms of evidence do not necessarily establish translational readiness. This evidence-mapping review examines how the literature connects material characterization, biological identity, barrier interactions, biodistribution, intracellular delivery, pharmacological efficacy, safety, manufacturing control, and clinical or regulatory translation. A systematic evidence-mapping approach was used to identify eligible peer-reviewed literature, classify delivery-system technologies, chart development stages and validation contexts, and distinguish evidence presence from evidence quality, connectedness, or readiness. The mapped landscape indicates comparatively concentrated evidence around nanoparticle characterization, cancer-oriented delivery, lipid-based carriers, tumor transport, and microfluidic formulation. Evidence becomes less continuous when studies must connect bulk tissue accumulation with target-cell access, cellular uptake with functional intracellular release, preclinical efficacy with clinically relevant safety, or laboratory formulation with reproducible large-scale manufacture. Protein-corona prediction, biohybrid carriers, stimuli-responsive systems, endosomal escape, extrahepatic targeting, and patient-selection biomarkers represent important but variably validated clusters. Across technologies, translational maturity is limited less by the absence of promising mechanisms than by discontinuities between analytical, biological, pharmacological, manufacturing, and human-relevant evidence. The review therefore proposes a structured evidence landscape in which favorable findings remain bounded by the model, product, route, disease context, and validation level examined. The principal implication is that translational readiness should be interpreted as an evidence-linked, product-specific condition rather than as an automatic consequence of nanoscale design, targeting functionality, publication activity, or isolated preclinical success.