Ultrasound-Assisted Nanoemulsification for Food and Nutraceutical Applications: Mechanisms, Formulation Strategies, and Translational Challenges.

Ultrasound-assisted nanoemulsification has emerged as a versatile platform for producing food-grade nanoemulsions with enhanced stability and improved delivery potential of lipophilic bioactives. This review offers a critical, integrated analysis of the mechanistic principles, formulation parameters, applications, and translational challenges of ultrasound-assisted nanoemulsification for food and nutraceutical applications. The review synthesizes findings on cavitation-driven droplet disruption, key operational parameters, and formulation factors governing nanoemulsion formation and performance. It also discusses applications in bioactive delivery, essential-oil-based preservation, and protein-based carrier systems. Key findings reveal that ultrasound can effectively produce sub-200 nm droplets through mechanical cavitation-driven disruption. However, excessive processing provides limited size reduction, whereas formulation composition determines emulsion stability and functionality. The review identifies that improved in vitro bioaccessibility does not constitute evidence of enhanced systemic bioavailability. Droplet size is a conditional rather than universal predictor of gastrointestinal delivery, and the interface paradox represents a fundamental design challenge that requires rational interfacial engineering. Persistent barriers to industrial translation include inconsistent parameter reporting, non-uniform cavitation fields during scale-up, and limited validation in complex food matrices. Future research priorities include standardized reporting of acoustic parameters, in vivo validation linking bioaccessibility with systemic bioavailability, pilot-scale studies, and interfacial engineering strategies to resolve the stability-digestibility trade-off.