Redox-responsive thiolated hyaluronic acid hydrogel for probiotic encapsulation: Fabrication, characterization, and gastrointestinal stability.

To address the challenges associated with oral probiotic delivery in the treatment of inflammatory bowel disease (IBD), a hydrogen sulfide (H2S)-responsive hydrogel delivery system was developed. Hyaluronic acid was modified with cysteamine hydrochloride to yield thiolated hyaluronic acid (HA-SH). Limosilactobacillus fermentum CECT5716, a well-documented probiotic strain, was utilized as a model bacterium to prepare the probiotic-loaded hydrogel (HA-SH-P). The successful synthesis of HA-SH was confirmed by 1H NMR, FTIR, and UV spectroscopy, with the sulfhydryl content determined to be 0.88 mmol/g. Scanning electron microscopy confirmed the uniform dispersion of probiotics within the hydrogel matrix. Reduction-responsive experiments demonstrated that the HA-SH system facilitated controlled release of L. fermentum CECT5716 in the presence of sulfide ions. In vitro assays revealed a 3.09 log CFU/mL increase in probiotic viability compared to free bacteria. The hydrogel was evaluated for in vivo safety and was shown to be biologically safe. This redox-responsive hydrogel holds significant potential for targeted IBD therapy and may serve as a valuable platform for the development of probiotic-loaded hydrogel systems in biomedical applications.