Vitamin E (VE), primarily α-tocopherol, is considered an important lipid-soluble vitamin and biological antioxidant. Its unique chemical structure enables it to effectively scavenge free radicals during lipid peroxidation chain reactions, thereby protecting cellular membrane integrity and retarding lipid oxidation (Mujica-Álvarez et al., 2020; Na et al., 2021). In the food industry, VE is primarily employed to extend the shelf life of fat-rich products. For example, it is used as a food additive to retard lipid oxidation in fish sausage. Furthermore, in natural oil systems like olive oil, VE is typically the first endogenous antioxidant oxidized to protect unsaturated fatty acids from oxidation (Rastrelli, Passi, Ippolito, Vacca, & de Simone, 2002; Zambrano-Zaragoza et al., 2014). The natural VE content of many modern foods can be lost during food processing. Therefore, the deficiency in dietary intake can be addressed by reintroducing it to the food or by fortifying food products with inherently low VE levels. For example, VE is incorporated into beverages as a component of antioxidant nutrient supplements (McClements & Decker, 2018). Furthermore, VE is known to counteract ultraviolet-induced photoaging in skincare products. Additionally, it is utilized in the pharmaceutical field, where its applications are based on core mechanisms, including its antioxidant, anti-inflammatory, and cell-regulating properties (Öztürk, 2017).

However, VE is highly susceptible to degradation when influenced by external factors such as light, heat, oxygen, and metal ions. This chemical instability severely limits its application and efficacy across various products (Pignitter, Grosshagauer, & Somoza, 2019). For example, 13.9% of VE is lost after 6 min at 110°C, whereas 23.8% of VE is lost after the same period at 140 °C (Sabliov et al., 2009). In an aerobic environment, the stability of VE is halved for every 10°C increase in temperature when the temperature exceeds 40°C (Bruscatto, Pestana-Bauer, Otero, & Zambiazi, 2019). Even at ambient temperature, the degradation of VE is continuously observed. In olive oil, where VE is the first antioxidant oxidized, its content can be reduced by up to 92% after 12 months of storage in half-filled bottles (Rastrelli et al., 2002). The degradation of VE leads to a series of downstream issues: it is responsible for reduced nutritional value and deterioration of product flavor in foods. Phenomena like phase separation and flocculation occurred in beverages (McClements & Decker, 2018). In cosmetic products, a significant decline in product efficacy appeared (Lukić, Pantelić, & Savić, 2021). In the pharmaceutical field, higher dosages are required to achieve therapeutic effects due to the low bioavailability, while long-term ingestion of large doses of VE may be associated with adverse reactions (Miller et al., 2005; Reboul, 2017).

To overcome the inherent limitations of VE regarding water solubility, bioavailability, and chemical stability, various stabilization techniques have been explored. Among these, nanoemulsion technology is considered a critical solution (Banasaz, Morozova, Ferrentino, & Scampicchio, 2020). Nanoemulsions are dispersion systems typically characterized by droplet sizes (DS) ranging from 20 to 500 nm. Due to their extremely small and uniformly distributed droplets, they are regarded as being highly stable kinetically (Li et al., 2025; Xu et al., 2023). When VE is encapsulated within the oil droplets in nanoemulsions, an effective physical and chemical protective barrier is provided for this lipid-soluble bioactive substance. The interfacial membrane formed by the nanoscale oil droplets is capable of effectively hindering the permeation of oxygen and oxidants from the aqueous phase into the droplet core, thereby protecting VE from oxidative degradation (Neyestani, Raziabad, Gilani, & Shariatifar, 2021). Furthermore, the substantial specific surface area of the nanoscale droplets is known to significantly promote the release and absorption of VE in the digestive tract, resulting in a substantial increase in its bioavailability (Choi & McClements, 2020).

Ultrasonic emulsification, as an efficient, controllable, and scalable preparation technology, has been widely applied in the field of nanoemulsion production (Shen, Sun, Pan, Yu, & Zhou, 2024; Sneha & Kumar, 2022). Its core mechanism is based on the acoustic cavitation effect produced when ultrasound waves propagate through a liquid. High-intensity ultrasonic waves will produce tiny cavitation bubbles, which rapidly grow and collapse under the alternating positive and negative pressure of the sound field, eventually undergoing violent implosion. This implosion process generates extremely high localized temperatures and pressures (about 5000 K and 50 MPa) inside and around the bubbles, along with powerful microjets and shear forces (Wu, Abramova, Nikonov, & Cravotto, 2020). These intense physical effects are utilized to effectively break down large droplets into the nanoscale, forming emulsions with small DS, uniform distribution, and excellent physical stability (Dong, Delacour, Carogher, Udepurkar, & Kuhn, 2020; Liu, Yang, Dong, Yao, & Chen, 2023).

However, some inherent limitations have been observed in the conventional emulsification with an ultrasonic probe (USE(P)) and an ultrasonic bath (USE(B)), e.g., a significant energy gradient exists while using USE(P). On the one hand, the higher cavitation intensity around the ultrasonic probe tip causes over-processing and severe oxidation. On the other hand, the oil droplets away from the probe tip cannot be completely emulsified (O'Sullivan, Murray, Flynn, & Norton, 2015). Similarly, USE(B) also exhibits low energy transfer efficiency and a noticeable standing wave effect, resulting in non-uniform emulsification (Adamou, Harkou, Villa, Constantinou, & Dimitratos, 2024). These intrinsic defects make it challenging for traditional USE methods to achieve excellent physical stability while effectively controlling the chemical degradation of VE. According to Hashtjin et al., improper ultrasonic parameters can lead to an increase in polydispersity index (PDI) due to uneven energy distribution. A nanoemulsion with an average DS of 50 nm and a PDI of 0.65 was prepared under conditions of 76% amplitude and 138 s treatment time. However, when the amplitude was increased to 94% while the treatment time was maintained at 138 s, the PDI significantly increased to above 0.76, even though the average DS was reduced to 26 nm (Hashtjin & Abbasi, 2015). It further confirms the negative impact of non-uniform energy distribution on emulsion dispersity. Another commonly recognized negative impact of traditional ultrasonic treatment is associated with the extreme conditions generated during cavitation bubble implosion, causing the thermolysis of water molecules and the formation of highly active reactive oxygen species (ROS), such as hydroxyl radicals and hydrogen peroxide (H2O2) (Guo et al., 2011). These highly active ROS can react with VE molecules to different extents, causing irreversible oxidative degradation of VE during the emulsification process and subsequent storage. Fernandes et al. reported that VE content in avocado was reduced by up to 79% due to ultrasonic treatment (Fernandes, Oliveira, Gomes, & Rodrigues, 2016).

To address the aforementioned challenges, a novel temperature-controlled ultrasonic tube-in-tube reactor (USTIT) was adopted in this study. Its unique continuous-flow design and uniform acoustic field distribution ensure that all feedstocks can be subjected to ultrasonic emulsification with uniform cavitation intensity and a controlled residence time. This strategy aims at overcoming the drawbacks of over-processing and under-processing using traditional USE methods, minimizing the oxidative degradation of VE in nanoemulsions, and boosting the physical and chemical stability of VE nanoemulsions during storage. The influence of emulsions' formulation (emulsifier type, aqueous-to-oil (A/O) ratio, protective agents, etc.) and ultrasonic processing parameters (ultrasonic power, temperature, flow rate, etc.) on the physical and chemical stability of the VE nanoemulsions is systematically investigated. The results are expected to provide a theoretical basis for the industrial continuous production of nanoemulsions containing high-value lipid-soluble bioactive substances.