Hydrogel-Based Delivery Systems for Targeted Probiotic Release and Colonization: From Design Principles to Health Outcomes

Abstract

Probiotics exert profound health benefits via the modulation of the intestinal microbiota. However, the efficacy of orally administered probiotics is severely constrained by a cascade of physiological barriers, including gastric acid inactivation, suboptimal intestinal release, and inadequate mucosal colonization. In response to these challenges, hydrogel-based delivery platforms have garnered considerable interest as versatile carriers capable of providing protective encapsulation, enabling spatiotemporally controlled release, and augmenting intestinal retention. This narrative review presents recent progress in the design and application of hydrogel-based oral delivery systems tailored for targeted probiotic release and effective colonization. First, the key gastrointestinal obstacles to successful probiotic delivery are delineated. Hydrogel design parameters are then critically appraised, with particular emphasis on material selection and network design. The underlying release mechanisms are subsequently examined. These encompass pH-responsive, enzyme-triggered, and inflammation-responsive modalities. Emerging colonization-enhancing strategies are discussed in detail. These include mucoadhesive hydrogel architectures and the nascent paradigm of “living hydrogels” functioning as dynamic bioreactors. The translational potential of these systems for health management is illustrated through applications in inflammatory bowel disease, colorectal cancer, and gut–brain axis modulation. Finally, key challenges in manufacturing, viability, and translational feasibility are evaluated. These include regulatory, safety, and encapsulation-related constraints. To address these, multi-responsive platforms, machine learning-assisted design, and synbiotic hydrogels are proposed. These hydrogels synergize with probiotics to target dysbiosis and repair mucosal damage for improved gastrointestinal health management.