Minimum Charged State – Exploring Polyampholyte‐Salt Interactions and Its Impact on Gelatin‐Alginate Hydrogels

ABSTRACT Electrostatic interactions (salts) are pivotal in tuning the conformations of charged polymers. This article delves into salt interactions of gelatin, a polyampholyte with pH‐dependent conformations. At the isoelectric point (IEP), attractive interactions among similarly charged groups of gelatin result in a collapsed conformation. At other pH values, gelatin assumes an extended state. Interestingly, this state can be transformed to an IEP‐like state through salt‐induced screening, resulting in a minimally charged state. The existence and behavior of such states remain largely unexplored. In principle, this untapped feature should be relevant for any protein (polyampholyte) in the presence of salt ions and is worth investigating. Here, Hofmeister salts are employed to achieve this minimum charged state (MCS). Additionally, the impact of MCS on gelatin‐alginate hydrogel properties was examined to investigate the role of polymer conformation in enhancing drug release and rheological properties. DLS was employed to investigate interactions in the system and correlated to drug release profile, gel strength, crosslinking density, mesh size, and self‐healing properties of hydrogels. Our findings demonstrate that hydrogel properties are predominantly governed by electrostatic interactions, with chaotropes exhibiting better release, gel strength, crosslinking density, and mesh size at MCS, and kosmotropes at non‐MCS. However, MCS exhibited better self‐healing properties in all cases.