%0 Journal Article
%T Drug nanoclusters formed in confined nano-cages of CD-MOF: dramatic enhancement of solubility and bioavailability of azilsartan
%A Caifen Wang
%A Guoqing Zhang
%A Jiwen Zhang
%A Li Wu
%A Liu Zhang
%A Ming Yang
%A Ruxandra Gref
%A Vikramjeet Singh
%A Wei Qin
%A Wei Zhang
%A Weifeng Zhu
%A Xiaoxiao Hu
%A Yuanzhi He
%J Archive of "Acta Pharmaceutica Sinica. B".
%D 2019
%R 10.1016/j.apsb.2018.09.003
%X Tremendous efforts have been devoted to the enhancement of drug solubility using nanotechnologies, but few of them are capable to produce drug particles with sizes less than a few nanometers. This challenge has been addressed here by using biocompatible versatile ¦Ã-cyclodextrin (¦Ã-CD) metal-organic framework (CD-MOF) large molecular cages in which azilsartan (AZL) was successfully confined producing clusters in the nanometer range. This strategy allowed to improve the bioavailability of AZL in Sprague¨CDawley rats by 9.7-fold after loading into CD-MOF. The apparent solubility of AZL/CD-MOF was enhanced by 340-fold when compared to the pure drug. Based on molecular modeling, a dual molecular mechanism of nanoclusterization and complexation of AZL inside the CD-MOF cages was proposed, which was confirmed by small angle X-ray scattering (SAXS) and synchrotron radiation-Fourier transform infrared spectroscopy (SR-FTIR) techniques. In a typical cage-like unit of CD-MOF, three molecules of AZL were included by the ¦Ã-CD pairs, whilst other three AZL molecules formed a nanocluster inside the 1.7£¿nm sized cavity surrounded by six ¦Ã-CDs. This research demonstrates a dual molecular mechanism of complexation and nanoclusterization in CD-MOF leading to significant improvement in the bioavailability of insoluble drugs
%K ¦Ã-Cyclodextrin metal-organic framework
%K Nanoclusterization
%K Azilsartan
%K Mechanism
%K Solubility
%K Bioavailability
%K Molecular modeling
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361728/