Drug nanoclusters formed in confined nano-cages of CD-MOF: dramatic enhancement of solubility and bioavailability of azilsartan
文献类型：期刊论文
| 作者 | He, Yuanzhi1,2; Zhang, Wei2,3; Guo, Tao2; Zhang, Guoqing2; Qin, Wei1,2; Zhang, Liu2; Wang, Caifen2; Zhu, Weifeng1; Yang, Ming1; Hu, Xiaoxiao2 |
| 刊名 | ACTA PHARMACEUTICA SINICA B
 |
| 出版日期 | 2019 |
| 卷号 | 9期号:1页码:97-106 |
| 关键词 | gamma-Cyclodextrin metal organic framework Nanoclusterization Azilsartan Mechanism Solubility Bioavailability Molecular modeling |
| ISSN号 | 2211-3835 |
| DOI | 10.1016/j.apsb.2018.09.003 |
| 通讯作者 | Wu, Li(track_wuly@163.com) ; Gref, Ruxandra(ruxandra.gref@u-psud.fr) ; Zhang, Jiwen(jwzhang@simm.ac.cn) |
| 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 y-cyclodextrin (gamma -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 gamma-CD pairs, whilst other three AZL molecules formed a nanocluster inside the 1.7 nm sized cavity surrounded by six gamma-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. (C) 2019 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| WOS关键词 | METAL-ORGANIC FRAMEWORKS ; DELIVERY ; STABILITY ; ENCAPSULATION ; NANOCRYSTALS ; FORMULATION ; CURCUMIN ; PHASE ; GEL |
| 资助项目 | National Science and Technology Major Projects for the Major New Drugs Innovation and Development (China)[2018ZX09721002-009] ; Strategic Priority Research Program of Chinese Academy of Sciences[XDA12050307] ; National Natural Science Foundation of China[81430087] ; China Postdoctoral Science Foundation[2017M610284] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000457201700009 |
| 出版者 | INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/290616]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Wu, Li; Gref, Ruxandra; Zhang, Jiwen |
| 作者单位 | 1.Jiangxi Univ Tradit Chinese Med, Key Lab Modern Preparat TCM, Minist Educ, Nanchang 330004, Jiangxi, Peoples R China 2.Chinese Acad Sci, Ctr Drug Delivery Syst, Shanghai Inst Mat Med, Shanghai 201210, Peoples R China 3.Shanghai Inst Technol, Sch Chem & Environm Engn, Shanghai 201418, Peoples R China 4.Univ Paris Saclay, Univ Paris Sud, UMR CNRS 8214, Inst Sci Mol Orsay, F-91400 Orsay, France 5.Yantai Univ, Sch Pharm, Key Lab Mol Pharmacol & Drug Evaluat, Minist Educ, Yantai 264005, Peoples R China |
| 推荐引用方式 GB/T 7714 | He, Yuanzhi,Zhang, Wei,Guo, Tao,et al. Drug nanoclusters formed in confined nano-cages of CD-MOF: dramatic enhancement of solubility and bioavailability of azilsartan[J]. ACTA PHARMACEUTICA SINICA B,2019,9(1):97-106. |
| APA | He, Yuanzhi.,Zhang, Wei.,Guo, Tao.,Zhang, Guoqing.,Qin, Wei.,...&Zhang, Jiwen.(2019).Drug nanoclusters formed in confined nano-cages of CD-MOF: dramatic enhancement of solubility and bioavailability of azilsartan.ACTA PHARMACEUTICA SINICA B,9(1),97-106. |
| MLA | He, Yuanzhi,et al."Drug nanoclusters formed in confined nano-cages of CD-MOF: dramatic enhancement of solubility and bioavailability of azilsartan".ACTA PHARMACEUTICA SINICA B 9.1(2019):97-106. |
入库方式： OAI收割
来源：上海药物研究所
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