Hierarchical design of hybrid carriers to control nutrient fate

For decades, nutrient delivery system design has been constrained by a fundamental trade-off: Enhancing stability is often associated with reduced bioavailability, and vice versa . This review presents a hierarchical, multi-scale design strategy for hybrid materials. At the molecular level, thermodynamic control of binding interactions, such as through precise chelation chemistry, maintains bioactive compounds in a soluble yet protected state. Moving to the microscale, engineering of porosity, tortuosity, and interfacial properties creates intelligent, stimuli-responsive barriers that remain inert until encountering their target physiological environment. The macroscopic architecture, in turn, is tailored for mechanical resilience against digestive forces while promoting desirable interactions with mucosal surfaces. The field is now leveraging computational screening and machine learning to navigate vast material spaces, accelerating the discovery of novel constructs with optimized biological interfaces. The future points toward truly “smart” systems capable of targeted release, where the carrier itself may contribute synergistic health benefits beyond mere protection. This evolution from empirical formulation to the rational design of matter across scales effectively renders the old stability-bioavailability compromise obsolete.