Tang Lei, Feng Yinan, Bian Yifei, Sun Zhixiong, Ding Qiaoce, Chen Dongying, Wang Jian-Rong, Mei Xuefeng
Pharmaceutical Analytical & Solid-State Chemistry Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Mol Pharm. 2025 Nov 3;22(11):6907-6919. doi: 10.1021/acs.molpharmaceut.5c00851. Epub 2025 Sep 9.
Phytosterols are a class of natural steroids found in various plants. Commercially available phytosterols (PS) are primarily extracted from the deodorized distillate of soybean oil and consist predominantly of β-sitosterol with smaller amounts of stigmasterol and campesterol. Numerous studies have consistently demonstrated the significant lipid-lowering activity of PS. However, the application of PS is limited due to their low oral bioavailability. To enhance the water solubility and in turn the absorption of PS at the molecular level, microcapsule-like cocrystals were designed using bile acids via hydrogen bonding. As expected, four microcapsule-like cocrystals were successfully prepared: β-sitosterol with cholic acid (CA) and chenodeoxycholic acid (CDCA), and PS with CA and CDCA. The cocrystal of PS with CA (PS-CA) was selected for further investigation, and the results demonstrated that PS-CA exhibited significantly enhanced solubility and markedly improved oral bioavailability . Specifically, the AUC of PS-CA was 6 times that of PS, while the was 4 times. Moreover, as a result of the improved bioavailability of PS, PS-CA showed superior lipid-lowering activity.
植物甾醇是一类存在于多种植物中的天然甾体化合物。市售的植物甾醇（PS）主要从大豆油脱臭馏出物中提取，主要成分是β-谷甾醇，还有少量的豆甾醇和菜油甾醇。大量研究一致表明PS具有显著的降血脂活性。然而，由于其口服生物利用度低，PS的应用受到限制。为了在分子水平上提高PS的水溶性进而提高其吸收，通过氢键作用利用胆汁酸设计了微胶囊状共晶体。正如预期的那样，成功制备了四种微胶囊状共晶体：β-谷甾醇与胆酸（CA）和鹅去氧胆酸（CDCA），以及PS与CA和CDCA。选择PS与CA的共晶体（PS-CA）进行进一步研究，结果表明PS-CA的溶解度显著提高，口服生物利用度明显改善。具体而言，PS-CA的AUC是PS的6倍，而 是PS的4倍。此外，由于PS生物利用度的提高，PS-CA表现出卓越的降血脂活性。
