drugnanoclustersformedinconfinednanocagesofcdmofdramaticenhancementofsolubilityandbioavailabilityofazilsartan

	drugnanoclustersformedinconfinednanocagesofcdmofdramaticenhancementofsolubilityandbioavailabilityofazilsartan
	Yuanzhi He 1; Wei Zhang 2; Tao Guo 2; Guoqing Zhang 2; Wei Qin 1; Liu Zhang 2; Caifen Wang 2; Weifeng Zhu 1; Ming Yang 1; Xiaoxiao Hu 2
刊名	药学学报英文版
	2019
卷号	000 期号:001 页码:97
关键词	γ-Cyclodextrin metal-organic framework Nanoclusterization Azilsartan Mechanism Solubility Bioavailability Molecular modeling
ISSN号	2211-3835
英文摘要	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 γ-cyclodextrin(γ-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–Dawley 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 γ-CD pairs, whilst other three AZL molecules formed a nanocluster inside the 1.7 nm sized cavity surrounded by six γ-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.
资助项目	[National Science and Technology Major Projects for the Major New Drugs Innovation and Development (China)] ; [Strategic Priority Research Program of Chinese Academy of Sciences] ; [National Natural Science Foundation of China] ; [China Postdoctoral Science Foundation]
语种	英语
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/284118]
专题	中国科学院上海药物研究所
作者单位	1.教育部 2.中国科学院上海药物研究所 3.上海应用技术大学 4.Institut des Sciences Moléculaires d'Orsay, Université Paris-Sud, Université Paris-Saclay, France
推荐引用方式 GB/T 7714	Yuanzhi He,Wei Zhang,Tao Guo,et al. drugnanoclustersformedinconfinednanocagesofcdmofdramaticenhancementofsolubilityandbioavailabilityofazilsartan[J]. 药学学报英文版,2019,000(001):97.
APA	Yuanzhi He.,Wei Zhang.,Tao Guo.,Guoqing Zhang.,Wei Qin.,...&Jiwen Zhang.(2019).drugnanoclustersformedinconfinednanocagesofcdmofdramaticenhancementofsolubilityandbioavailabilityofazilsartan.药学学报英文版,000(001),97.
MLA	Yuanzhi He,et al."drugnanoclustersformedinconfinednanocagesofcdmofdramaticenhancementofsolubilityandbioavailabilityofazilsartan".药学学报英文版 000.001(2019):97.