Fabrication Of Supersaturated Self-emulsifying Nanoemulsion For Nobiletin And Bioaccessibility Evaluation

A large class of hydrophobic active compounds like natural polymethoxyflavones(PMFs) are involved in functional food ingredients. The high hydrophobicity and melting point result in their poor water-solubility and high crystallinity, leading to their low oral bioavailability. How to improve their hydrophilicity and further enhance their bioavailability has become a critical issue to be solved. Nanoemulsion delivery systems can be utilized to improve the dissolution property of hydrophobic functional components, enhancing their oral efficiency. Meanwhile, the thermodynamic activity generated by supersaturated state might also increase their oral absorption efficiency. Therefore, both nanoemulsion delivery system and supersaturation state were combined in this thesis. Nobiletin(Nob) with crystalline and low water-solubility was selected as one of the typical PMFs. At first, the dissolution and crystallization behavior of Nob in different solvents and oil phases were investigated to provide information to design nanoemulsions with high loading efficiency and stability. Then, the Nob-load nanoemulsions were prepared by spontaneous emulsification and the stability and influence factors were studied. Furthermore, hydroxypropyl methylcellulose(HPMC) addition and heat treatment were applied to inhibit the crystallization and separation of supersaturated Nob in nanoemulsions. Finally, the bioaccessibility of Nob in different nanoemulsion systems was evaluated using a simulated gastrointestinal model. The information obtained will benefit the rational design of food-grade delivery systems for hydrophobic and crystallographic bioactive compounds, promoting the development of functional food ingredients industry.The main results are as follows: 1. The effects on dissolution and crystallization behavior of Nob were investigated. 1 wt% hydrophilic polymers were added to improve the low solubility of Nob in water at room temperature, and HPMC was found to be the most effective and increased by 1.3 times. The solubility of Nob in medium chain triglycerides(MCT) was as 2.3 times as that in bean oil, indicating that the chain of triglycerides had effects on the Nob solubility in oil. Solubility in pure non-ionic surfactant(Tween80) was up to 43.43 m M, which was as 3.7 and 634.1 times as that in MCT and water respectively, while solubility in 1 wt% anionic surfactants solution(sodium dodecyl sulfate, SDS) was 4.26 m M that was 26.9 times as that in 1 wt% HPMC. The the nucleation and crystal growth process of supersaturated Nob in oil phases depended on oil type, Nob concentration, and storage temperature. The results showed that the rate of nucleation and crystal growth was faster at higher initial Nob concentration and instead of being effected by oil type. The lag-time before rapid crystallization was observed appeared to be shorter at 25 oC than at 4 oC or 37 oC. High storage temperature was benefit to increase the equilibrium solubility. The morphology of Nob was investigated by polarized light microscopy, which showed the image of needle-like crystals clustered into bundles.2. The Nob-load emulsions was prepared by spontaneous emulsification, and the stability of Nob in the system was improved. The optimized ratio of MCT, surfactant(Span20 : Tween80 = 1:3; HLB 13.4) and water was 5 wt%, 10 wt% and 85 wt%. The presence of HPMC in aqueous phase improved the retention of Nob in nanoemulsions, despite of the order of addition. Heat treatment of nanoemulsions not only altered the droplet size and appearance but also increased the stability of supersaturated Nob in nanoemulsion. The combination of HPMC addition and heat treatment increased the retention time of Nob in nanoemulsions. In the presence of HPMC, the Nob remained soluble in heating nanoemulsions with initial concentration of 4.5 mg/m L, and the stable time extended for 12 h when it was present at 6.0 mg/m L. The result was important to improve the bioavailibility of Nob in emulsion system.3. The influence of different nanoemulsions on the bioaccessibility of Nob after passing through the simulated gastrointestinal tract was examined. Results indicated that the initial content of Nob, addition of HPMC and heat treatment had no significant influence on the oil digestion. The nanoemulsions were not obviously disrupted despite of some changes of after exposure to the simulated mouth and stomach conditions. However, the lipid phase was digested by lipase and the emulsion was disrupted after exposure to small intestinal environment. Neither HPMC addition nor heat treatment affected the bioaccessibility of Nob with relatively low initial supersaturation degree, but heat treatment did improve the bioaccessibility of Nob by 57.84% when initial supersaturation was relatively high. Therefore, heat treatment was an effective method to improve the bioaccessibility of supersaturated Nob in nanoemulsions.