Malektaj, HaniyehHaniyehMalektajDrozdov, AlekseyAlekseyDrozdovGurikov, PavelPavelGurikovSchroeter, BaldurBaldurSchroeterFini, ElhamElhamFiniChristiansen, Jesper De C.Jesper De C.Christiansen2025-07-292025-07-292025-07-16Journal of Drug Delivery Science and Technology 112: 107275 (2025)https://hdl.handle.net/11420/56520Controlled delivery of hydrophilic drugs remains a major challenge due to their high water solubility and rapid diffusion. This study aims to address this issue by developing alginate–montmorillonite (MMT) nanocomposite hydrogels crosslinked with different multivalent cations (Fe³⁺, Cu²⁺, Sr²⁺, and Ca²⁺) and systematically analyzing their effects on drug encapsulation and release. Hydrogels were evaluated for structural morphology using Scanning Electron Microscopy (SEM), while swelling studies were used to determine mesh size (ranging from 34 to 58 nm) and diffusion coefficients. Drug release was quantified at pH 7 and 37 °C using UV/Vis spectroscopy and fitted to mathematical models to identify the release mechanism. The Fe³⁺-crosslinked hydrogel showed the highest encapsulation efficiency (98 %) and the slowest release rate. By correlating the formation constants of each cation with their diffusivity, a predictive model was developed to guide formulation modifications for tuning the release profile. These results demonstrate that cation selection significantly influences the physicochemical properties of alginate–MMT hydrogels and offer a quantitative framework for designing tunable drug delivery systems based on nanocomposites hydrogel.en2588-89432025Ed. de SantéAlginate | Delivery systems | Hydrogel | Mesh size | Montmorillonite | Multivalent cationsTechnology::600: TechnologyJournal Article10.1016/j.jddst.2025.107275Journal Article