Comparative review of colloidal delivery strategies for hydrophobic bioactives: Pickering emulsions, emulsion gels, and nanogels

Hydrophobic bioactives (e.g., curcumin, carotenoids, polyphenols) offer substantial health benefits but are fundamentally limited by poor water solubility, environmental instability, and low gastrointestinal bioavailability. While colloidal delivery systems help overcome these barriers, current research typically isolates and optimizes individual platforms, neglecting the broader conflict between structural stability and digestive bioaccessibility. This review systematically compares three hierarchical spatial confinement strategies-two-dimensional Pickering emulsions (PEs), three-dimensional macroscopic emulsion gels (EGs), and three-dimensional nanogels (NGs)-to clarify their structure-function relationships. We identify a fundamental tradeoff: structural features that maximize environmental stability often create severe steric hindrance, restricting enzyme permeability and lipid micellization. Consequently, release mechanisms vary fundamentally across platforms: PEs rely on interfacial desorption (first-order kinetics), EGs use continuous matrix diffusion (Ritger-Peppas model) for sustained release, and NGs leverage stimuli-responsive dynamic dissociation. Additionally, we map compound-specific compatibility requirements, showing that curcumin needs interfacial physical masking against alkaline hydrolysis, carotenoids require nanoscale amorphous confinement to prevent photo-oxidation, and polyphenols depend on dynamic redox protection. To address current bottlenecks, we advocate shifting from "passive stabilization" to "digestion-responsive engineering." By examining critical hurdles like the lack of in vitro-in vivo correlation (IVIVC), scalability, and long-term nanotoxicity, this review provides a practical framework for designing next-generation delivery systems.