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

摘要

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 than20.00 ng/mL at pH 1.0 and pH 4.5,whilst its solubility increased to 20,074.30 ng/mL at pH 6.8 and129.58 ng/mL in water with a significant pH-dependence.The in vitro release profiles of STV from STV@CD-MOF(0.5:1)were pH-independent in distinct pH media and closed to be thoroughly released but no such release profiles were observed for STV@CD-MOF(1:1)owing to nanoclusters formation.The bioavailability of STV@CD-MOF(1:1)in rats was 8.67-fold higher than that of STV,and was1.32-and 1.27-fold higher than that of STV@CD and STV@CD-MOF(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.