Next-generation probiotic delivery: Engineering complex coacervation systems for targeted gut release and bioactive synergy

Abstract

Probiotics offer diverse health benefits, yet their efficacy is severely constrained by low viability during food processing, storage, and gastrointestinal transit. Complex coacervation, driven by electrostatic interactions between oppositely charged biopolymers, has emerged as a versatile encapsulation platform, but its recent evolution through integrated engineering strategies and co-delivery architectures has not been systematically reviewed. This review critically examines the design of complex coacervation systems for probiotic survival, analyzing synergistic technologies (drying, tableting, emulsification, crosslinking, and physical field) and co-delivery systems with bioactive compounds from an engineering perspective, with emphasis on protective mechanisms, formulation-process relationships, and translational bottlenecks. Complex coacervation provides a customizable, pH-responsive barrier that shields probiotics from thermal, oxidative, acidic, and bile stresses. Importantly, the physicochemical properties of coacervate networks, including polymer composition, crosslinking density, permeability, and swelling behavior, also determine gastrointestinal release profiles by allowing protection in the stomach while facilitating probiotic liberation under intestinal conditions. When integrated with complementary technologies, this barrier achieves hierarchical protection—drying for powder stability, tableting for macroscopic shielding, emulsification for multi-compartment architectures, crosslinking for mechanical reinforcement, and low-frequency static magnetic field for clean-label physical modulation. Co-delivery further preserves probiotic viability while enhancing bioactive bioavailability, unlocking synergistic gut-health benefits. Nevertheless, system performance remains highly formulation- and process-dependent, governed by polymer selection, charge balance, crosslinking density, drying regimes, and packaging. Translating these engineered systems into next-generation commercial products requires deeper mechanistic insights, standardized characterization, precise release kinetics, robust in vivo validation, and scalable manufacturing solutions.