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