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.
基金
financial support from the National Science Foundation for Young Scientists of China(No.81803441)
the National Science and Technology Major Projects for the Major New Drugs Innovation and Development(No.2018ZX09721002-009,China)
the National Natural Science Foundation of China(No.81873019)
the University Synergy Innovation Program of Anhui Province(GXXT-2020-025)
作者简介
Corresponding authors:Jiwen Zhang,Tel./fax:+862150805901,E-mail addresses:jwzhang@simm.ac.cn;Corresponding authors:Li Wu,Tel./fax:+862120231980,E-mail addresses:wuli@simm.ac.cn;Corresponding authors:Shuangying Gui,Tel./fax:+8655168129123,E-mail addresses:guishy0520@ahtcm.edu.cn;Equal contributions to this work:Xiaojin Chen;Equal contributions to this work:Tao Guo.
