Numerous studies have demonstrated that polymethoxyflavones (PMFs) have potential functional activities, including anti-inflammatory, anti-hyperprolactinemia, and anti-cancer. One molecule of PMF contains several methoxy groups that are connected to the flavone ring. This structure possesses a strong planar structure that resists the entry of water. The poor water-solubility of PMFs decreases their bioavailability and limits their application in designing functional foods. Herein, we fabricated a nanoemulsion stabilized by Maillard whey protein isolate conjugates (MWPI) and a Pickering emulsion stabilized by whey protein fibrils (WPF) to encapsulate PMFs and investigated their bioaccessibility. The nanoemulsion prepared by MWPI has better stability, and the loading amount of PMFs in the nanoemulsion after spray-drying reached 700 μg/g. Compared with free PMFs, the nanoemulsion showed a stronger inhibitory effect on MCF-7 and HepG2 cells. The main mechanism for the PMFs-loaded nanoemulsion to enter the cells was via pinocytosis for HepG2 and clathrin-mediated pits for MCF-7 cells. Besides, WPFs are potential emulsifiers with a highly pH-dependent structure. With an increase in pH from 2.0 to 5.0, the cross-sectional radius of the WPI fibrils increased from 2 to 8 nm. While with a further increase in the pH to 7.0, the fibrils decreased to a single strand. At all pH conditions, the WPI fibrils were effectively absorbed in the oil-water interface. The d<sub>4,3</sub> values of the WPFs-stabilized Pickering emulsions were around 70-80 μm. The loading of WPFs-stabilized Pickering emulsions could reach more than 100 mg/g, showing the high loading capacity. These studies provide a theoretical basis for developing emulsion-based delivery systems for PMFs.

Delivery of polymethoxyflavones (PMFs) using emulsions stabilized by whey proteins derived biomaterials

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