Postbiotic-loaded κ-carrageenan hydrogels double cross-linked with carboxymethyl cellulose and calcium ions

Abstract

Double cross-linked hydrogels made from sustainable, natural materials offer promising potential for drug delivery due to their pH-responsive behavior and favorable mechanical properties. Nevertheless, the application of petrochemical/synthetic components through complex techniques remains a main bottleneck to sustainability. Here, we report a novel convenient strategy to design an edible double network hydrogel from nature-inspired materials of x-carrageenan (xC) and carboxymethyl cellulose (CMC) to encapsulate indole-3-propionic acid (IPA) postbiotic, a biologically active ingredient, sensitive to acidic conditions of the stomach. The xC/CMC hydrogel displayed a tunable inter-connected porous network, controlled by varying Ca2+ concentrations. Increasing the calcium ion concentration influenced the hydrogel's equilibrium swelling rate. A moderate concentration of calcium ions facilitated the formation of a stable and well-organized hydrogel network, whereas higher concentrations disrupted the architecture, resulting in a less stable structure. This structural behavior is primarily governed by the interplay between hydrogen bonding and calcium ion-mediated cross-linking. Moreover, thermal gravimetric analysis and X-ray diffraction confirmed excellent excipient stability. These non-toxic, ecofriendly hydrogels successfully protected IPA in simulated gastric fluid and facilitated its release in simulated intestinal juice. This work provides new insights into the development of natural oral drug delivery systems with applications in pharmaceuticals and functional supplements, enhancing the stability, quality, gastric passage, and intestinal release of bioactive compounds.