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  1. Suthan R, Koo IK, Wang X, Goh KB
    Mol Pharm, 2026 Nov 02;23(11):5261-5271.
    PMID: 42969741 DOI: 10.1021/acs.molpharmaceut.6c00188
    Affinity hydrogels enable precise control of cargo release kinetics through specific, non-covalent interactions between the functionalized polymer network and therapeutic agents. Yet, how these interactions integrate with steric hindrance in the crosslinked network to determine cargo diffusivity, a critical kinetic parameter governing cargo-controlled release, remains poorly quantified. Here, we present a theoretical framework that explicitly bridges microscopic cargo-polymer interactions with macroscopic cargo release kinetics. Specifically, our approach delineates cargo diffusivity into two principal contributions: (i) binding interactions and (ii) steric hindrance, enabling a quantitative understanding of their interplay in defining cargo release performance. Increasing binding interactions, attractively, reduce diffusivity in a reverse sigmoidal fashion, transitioning from a steric- to a binding-controlled regime. Overall, we demonstrate how the interplay of microscopic forces governs cargo diffusivity within affinity hydrogels and, in turn, regulates cumulative cargo release at the macroscopic level, thereby bridging microscopic thermodynamic interactions with macroscopic cargo release kinetics, quantitatively.
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