Year: 2026
Type: preprint
Abstract: Alginate ionic hydrogels (AIGs) are widely used for cell and drug encapsulation, as well as across the food and pharmaceutical industries. However, unexplained phenomena—such as initial burst drug release, anomalous pH shifts, and the presence of counter-anions in the gel—are inadequately addressed by the scientific community and the conventional "egg-box" gelation model. In this work, we apply supramolecular theory to explain these stochastic behaviors, via evaluating AIGs under four core postulates for the theory: constitutional diversity and dynamics, spontaneous hierarchical assembly, and guest molecule accommodation. Using rheological, drug release, and spectroscopic (FTIR, XRD, EDX) analyses, we demonstrate that AIGs display all essential attributes of supramolecular materials. Results reveal that traditional calcium-alginate "egg-boxes" serve merely as primary structural units, whereas anion-driven secondary organization produces the material's hierarchical architecture. Consequently, altering the counter-anion of crosslinking calcium salts introduces constitutional diversity to tune various hydrogel 2 properties. The unexplained acidity in standard AIGs stems from spontaneous dissolution of environmental carbon dioxide during gelation, aligning with guest accommodation postulate of the theory. Replacing chloride anions with acetate or lactate promotes the conversion of dissolved carbon dioxide into insoluble mineral phases, neutralizing the gel's pH significantly. Similarly, switching from chloride to acetate mitigates initial burst drug release anomaly. Overall, this supramolecular framework provides deeper fundamental insights into alginate ionic gelation and opens new pathways for designing functional hydrogels.
Source: ChemRxiv
Authors: Subhasis Dash, Debasish Mishra
Institution: Vellore Institute of Technology University
Language: English
Subfield: Biomaterials
Field: Materials Science
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7204782141