In-vitro Delivery of Hydrophilic Drugs from Alginate–Montmorillonite Nanocomposite Hydrogels Cross-linked with Multivalent Cations

Alginate hydrogels cross-linked with various cations have numerous applications in targeted drug delivery. To enhance drug encapsulation efficiency, montmorillonite (MMT) clay nanoplatelets are incorporated into the alginate network. This study focuses on the effects of cations (Fe3+, Cu2+, Sr2+, and Ca2+) and concentration of MMT on the kinetics of the in-vitro release of diclofenac sodium from alginate–MMT nanocomposite hydrogels. Drug release is assessed in pH 7 solutions at 37 °C using a UV/Vis spectrophotometer. MMT affects the total drug release differently based on the formation constants of the cations. Drug release data are fitted to a model to identify the release mechanism. The release kinetics for alginate–MMT gels cross-linked with Fe3+ ions differ from those for gels bridged by Cu2+, Sr2+, and Ca2+ ions. Scanning Electron Microscopy analyzes the structural morphology of CO2-supercritical dried gels. Mesh size and diffusion coefficient are calculated from swelling tests. It is found that gel morphology, mesh size, egg-box junction reorganization, and drug release kinetics are strongly affected by the formation constant of cations. This study establishes a correlation between the formation constant and diffusivity, providing a predictive framework for diffusivity across different cations.