Theoretical framework for the kinetics and thermodynamics of cargo loading into affinity hydrogels

Despite significant attention directed toward affinity hydrogels as promising platforms for the controlled storage of therapeutic molecular cargo, the loading process remains incompletely understood. Notably, the direct link between surface-level binding interactions and bulk cargo uptake into these hydrogels remains unresolved. Here, we propose a coupling framework for the interplay between microscopic polymer–cargo interfacial interactions and macroscopic bulk uptake dynamics. In contrast to conventional empirical models, our approach explicitly integrates cargo–polymer interaction, enabling the identification of performance limits. Kinetically, we resolve the characteristic loading time as the system transitions between bulk-dominated and hydrogel-dominated kinetic regimes as a function of polymer–cargo binding affinity. Thermodynamically, we demonstrate that cargo permeability within the hydrogel is governed by the product of equilibrium partitioning and diffusivity, thereby revealing water-mediated modulation of cargo uptake efficacy. Collectively, by bridging microscale interactions with macroscale system behavior governing molecular cargo loading in affinity hydrogels, we re-highlight their potential as promising therapeutic storage as well as delivery platforms.