Tailored NaOH/phytic acid-driven method for fabricating carvacrol-loaded zein/trehalolipid nanoparticles with higher processing adaptability: Utilizing dual critical pH of wall and core materials

Encapsulating within zein/trehalolipid nanoparticles (Z/TL) via NaOH/phytic acid-driven method (PAPD) can improve water solubility and stability of carvacrol (CAR). However, this technique still has limitations including empirically determined parameters and potential risk of core material degradation. In this respect, we introduced a strategy of positioning dual critical pH based on specific attributes of wall and core materials. The finest alkalization endpoint for Z/TL was determined by monitoring conformational changes across pH 7–12. Meanwhile, the suitable pH of deprotonation was identified by assessing pH-dependent water solubility and chemical stability of CAR. Obtained information was applied to modify PAPD into PAPD’. The colloidal properties, encapsulation efficiency (EE), loading capability (LC), environmental stress resistance, and in vitro release behavior of nanoparticles prepared using PAPD’ and PAPD were systematically compared. The optimal alkalinization endpoint for Z/TL was determined to be pH 11.25. where the degree of hydrolysis would not increase further, but the acceleration of increase in aqueous solubility would reach its maximum. The optimal pH of deprotonation for CAR was pH 11, balancing high solubility with controllable degradation. PAPD’-nanoparticles exhibited a smaller size (99.36 nm), higher ζ-potential (−43.91 mV), and improved EE/LC (97.95 %/29.39 %). Enhanced stability, along with a sustained release profile were demonstrated. Consumption of NaOH/PA was also reduced while maintaining required efficacy. Overall, customized PAPD’ not only improves the processing adaptability and flexibility of fabricating protein-based nanoparticles but also provides a theoretical framework and practical paradigm for the rational design of nanocarriers for bioactive compounds.