Liu Gaodan, Liu Jingjian, Shao Ping, Kai Dan, Yang Liuqing, Sun Peilong, Feng Simin
Department of Food Science and Technology, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, People's Republic of China.
Key Laboratory of Food Macromolecular Resources Processing Technology Research (Zhejiang University of Technology), China National Light Industry, Hangzhou, Zhejiang 310014, People's Republic of China.
J Agric Food Chem. 2025 Jan 29;73(4):2596-2612. doi: 10.1021/acs.jafc.4c08428. Epub 2024 Dec 25.
Cholesterol (Cho) is commonly used to stabilize nanoliposomes; however, there is controversy on the relationship between Cho and health. In this study, we developed a novel multifunctional nanoliposome utilizing structurally similar sitogluside (SG) and dioscin (Dio) instead of Cho to anchor the phospholipid bilayer and synergistically modulate the membrane properties of the nanoliposome (DPPC or DOPC). The storage and gastrointestinal tract stability experiment demonstrated that the changes of physical and chemical properties, including the significantly reduced size and Dio retention rate of nanoliposomes synergistically modulated by SG and Dio compared to those of SG alone, regulated nanoliposomes. Moreover, the stabilization effect of DPPC nanoliposomes under the synergistic modulation of SG and Dio was superior to that of DOPC nanoliposomes. Similarly, in cell internalization and permeability studies, DPPC-sitogluside-dioscin (P-SG-Dio), which was synergistically modulated by SG and Dio, had the highest cellular uptake and transepithelial transport. In addition, compared with DPPC-cholesterol-dioscin (P-Cho-Dio) and free Dio, intragastric administration of P-SG-Dio for 14 days could effectively inhibit the activation of the NLRP3 inflammatory pathway in the kidney of hyperuricemic mice, exhibiting the best antihyperuricemic and anti-inflammatory effects. Fourier transform infrared and Raman spectroscopy results indicated that the glucose residues of SG and Dio synergistically modulate the membrane properties of nanoliposomes by forming hydrogen bonds between them and the polar heads of phospholipids. The absence of unsaturated bonds in DPPC led to the best effect of synergistic modulation, resulting in the superior membrane properties, stability, and bioavailability of P-SG-Dio. The finding offers valuable insight into the design and modification of nanoliposomes for the effective delivery of bioactive compounds.
胆固醇（Cho）常用于稳定纳米脂质体；然而，关于Cho与健康之间的关系存在争议。在本研究中，我们开发了一种新型多功能纳米脂质体，利用结构相似的谷甾糖苷（SG）和薯蓣皂苷（Dio）替代Cho来锚定磷脂双层，并协同调节纳米脂质体（二棕榈酰磷脂酰胆碱或二油酰磷脂酰胆碱）的膜性质。储存和胃肠道稳定性实验表明，与单独使用SG相比，由SG和Dio协同调节的纳米脂质体的物理和化学性质发生了变化，包括尺寸显著减小和Dio保留率提高，从而对纳米脂质体进行了调控。此外，在SG和Dio的协同调节下，二棕榈酰磷脂酰胆碱纳米脂质体的稳定效果优于二油酰磷脂酰胆碱纳米脂质体。同样，在细胞内化和通透性研究中，由SG和Dio协同调节的二棕榈酰磷脂酰胆碱-谷甾糖苷-薯蓣皂苷（P-SG-Dio）具有最高的细胞摄取和跨上皮转运。此外，与二棕榈酰磷脂酰胆碱-胆固醇-薯蓣皂苷（P-Cho-Dio）和游离Dio相比，胃内给予P-SG-Dio 14天可有效抑制高尿酸血症小鼠肾脏中NLRP3炎症通路的激活，表现出最佳的抗高尿酸血症和抗炎作用。傅里叶变换红外光谱和拉曼光谱结果表明，SG和Dio的葡萄糖残基通过在它们与磷脂极性头之间形成氢键来协同调节纳米脂质体的膜性质。二棕榈酰磷脂酰胆碱中不存在不饱和键导致协同调节效果最佳，从而使P-SG-Dio具有优异的膜性质、稳定性和生物利用度。这一发现为有效递送生物活性化合物的纳米脂质体的设计和修饰提供了有价值的见解。
