Structured systems based on natural saponins: a systematic review of design,

<jats:p>26 A systematic search was conducted in PubMed, Web of Science Core Collection, and Scopus for 27 studies published between 2015 and 2025. After duplicate removal, title/abstract screening, full-28 text retrieval, and eligibility assessment, 115 studies were included in the qualitative synthesis. 29 The evidence was organized into five thematic axes: self-assembly and biosurfactant function; 30 nanocarriers and controlled release; adjuvants and immunomodulation; sustainability and green 31 chemistry; and food and cosmetic applications. The reviewed literature shows that saponins are 32 not merely natural alternatives to synthetic surfactants, but multifunctional amphiphiles capable 33 of forming or stabilizing micelles, bicelles, vesicle-like systems, nanoemulsions, liposomes, 34 hydrogels, films, and hybrid carriers. Their performance depends on molecular structure, source, 35 concentration relative to the critical micelle concentration, pH, ionic strength, temperature, solvent 36 environment, and co-formulating materials. Despite strong evidence for nanoemulsions, micellar 37 systems, vaccine adjuvant platforms, and natural surfactant-based formulations, translation 38 remains limited by variability in saponin composition, incomplete standardization, scarce 39 comparative studies, and insufficient long-term safety or stability data. Overall, natural saponins 40 represent versatile structure-forming agents for sustainable, functional, and biologically active 41 systems, provided that future studies integrate chemical profiling, formulation metrics, 42 mechanistic interpretation, and application-specific safety assessment.</jats:p>