Simultaneous improvement to solubility and bioavailability of active natural compound isosteviol using cyclodextrin metal-organic frameworks

作者：Xiaojin Chen, Tao Guo, Kaikai Zhang, Jiacai Chen, Caifen Wang, Xiaohong Ren, Qin Wang, Yingchao Yang, Chongjing Liu, Wen Tan, Shuangying Gui, Li Wu, Jiwen Zhang · 发表于：Acta Pharmaceutica Sinica B · 年份：2021 · DOI：10.1016/j.apsb.2021.04.018 · 被引用次数：46 · 研究领域：Biochemical Analysis and Sensing Techniques、Metal-Organic Frameworks: Synthesis and Applications、Helicobacter pylori-related gastroenterology studies

Cyclodextrin metal-organic framework (CD-MOF) as a highly porous supramolecular carrier could be one of the solutions to the insolubility of isosteviol (STV). The solubility of STV was lower than 20.00 ng/mL at pH 1.0 and pH 4.5, whilst its solubility increased to 20,074.30 ng/mL at pH 6.8 and 129.58 ng/mL in water with a significant pH-dependence. The in vitro release profiles of STV from [email protected] (0.5:1) were pH-independent in distinct pH media and closed to be thoroughly released but no such release profiles were observed for [email protected] (1:1) owing to nanoclusters formation. The bioavailability of [email protected] (1:1) in rats was 8.67-fold higher than that of STV, and was 1.32- and 1.27-fold higher than that of [email protected] and [email protected] (0.5:1). Our results indicated that the inclusion mechanism played a primary role when STV in CD-MOF was at a low loading ratio, while the increasement in bioavailability at a high loading ratio, which was attributed to the nanocluster mechanism. This was confirmed by molecular simulation. In conclusion, CD-MOF is a promising system for STV loading, overcoming the insolubility and to improve the bioavailability of this natural compound.