Novel Nanoliposomes\nSynergistically Modulated by Sitogluside\nand Dioscin: Stability, Bioavailability, and Capacity To Alleviate\nHyperuricaemia

Cholesterol (Cho) is commonly used to stabilize nanoliposomes;\nhowever, there is controversy on the relationship between Cho and\nhealth. In this study, we developed a novel multifunctional nanoliposome\nutilizing structurally similar sitogluside (SG) and dioscin (Dio)\ninstead of Cho to anchor the phospholipid bilayer and synergistically\nmodulate the membrane properties of the nanoliposome (DPPC or DOPC).\nThe storage and gastrointestinal tract stability experiment demonstrated\nthat the changes of physical and chemical properties, including the\nsignificantly reduced size and Dio retention rate of nanoliposomes\nsynergistically modulated by SG and Dio compared to those of SG alone,\nregulated nanoliposomes. Moreover, the stabilization effect of DPPC\nnanoliposomes under the synergistic modulation of SG and Dio was superior\nto that of DOPC nanoliposomes. Similarly, in cell internalization\nand permeability studies, DPPC-sitogluside-dioscin (P-SG-Dio), which\nwas synergistically modulated by SG and Dio, had the highest cellular\nuptake and transepithelial transport. In addition, compared with DPPC-cholesterol-dioscin\n(P-Cho-Dio) and free Dio, intragastric administration of P-SG-Dio\nfor 14 days could effectively inhibit the activation of the NLRP3\ninflammatory pathway in the kidney of hyperuricemic mice, exhibiting\nthe best antihyperuricemic and anti-inflammatory effects. Fourier\ntransform infrared and Raman spectroscopy results indicated that the\nglucose residues of SG and Dio synergistically modulate the membrane\nproperties of nanoliposomes by forming hydrogen bonds between them\nand the polar heads of phospholipids. The absence of unsaturated bonds\nin DPPC led to the best effect of synergistic modulation, resulting\nin the superior membrane properties, stability, and bioavailability\nof P-SG-Dio. The finding offers valuable insight into the design and\nmodification of nanoliposomes for the effective delivery of bioactive\ncompounds.