MOF Capacitates Cyclodextrin to Mega-Load Mode for High-Efficient Delivery of Valsartan

doi:10.1007/s11095-019-2650-3

	MOF Capacitates Cyclodextrin to Mega-Load Mode for High-Efficient Delivery of Valsartan
	Zhang, Wei 1,2; Guo, Tao 2; Wang, Caifen 2; He, Yuanzhi 2; Zhang, Xi 3; Li, Guangyu 3; Chen, Yizhi 4; Li, Jun 4; Lin, Yangjing 4; Xu, Xu 1
刊名	PHARMACEUTICAL RESEARCH
	2019-08-01
卷号	36 期号:8 页码:13
关键词	Bioavailability cyclodextrin metal-organic framework solubility valsartan
ISSN号	0724-8741
DOI	10.1007/s11095-019-2650-3
通讯作者	Wu, Li(track_wuly@163.com) ; Zhang, Suxia(Zhangsx@sit.edu.cn) ; Zhang, Jiwen(jwzhang@simm.ac.cn)
英文摘要	PurposeTo investigate the mechanism of enhancing solubility and bioavailability of water-insoluble drug, valsartan(VAL), with beingmega-loaded by cyclodextrin metal organic framework (CD-MOF).MethodsVAL was successfully mega-loaded into CD-MOF by magnetic agitation of VAL in ethanolic solution. Characterizations including powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), synchrotron radiation-based Fourier transform-infrared spectroscopy (SR-FTIR) C-13 solid-state nuclear magnetic resonance spectroscopy ( C-13 SS-NMR), nitrogen gas adsorption, and small-angle X-ray scattering (SAXS) were carried out to confirm the mechanism and incorporation behavior of VAL in CD-MOF. Ball milling process combined with molecular modeling was also used to confirm the mechanism. Improvement of bioavailability in vivo was confirmed by pharmacokinetic experiment in beagles.ResultsAs a carrier with payload 150% higher than conventional CD complexation, CD-MOF included molecules of VAL as complexations in the chambers of (-CD)(2), and nanoclusters in the confined spherical cages of (-CD)(6) confirmed by SAXS and C-13 SS-NMR. Ball milling combined with molecular modeling inferred that the reduced release rate of the milled CD-MOF with ultrahigh drug payload was mainly due to the partial aggregation of the VAL nanoclusters. The molecules of VAL as nanoclusters in the cages of (-CD)(6) are critical in dramatically improving theapparent solubility (39.5-fold) and oral bioavailability (1.9-fold) of VAL in contrast to -CD inclusion.ConclusionsThe new understanding of drug nanoclusters in CD-MOF will help to design more efficient drug delivery systems using CD-MOF carrier with nanocavities.
资助项目	National Science and Technology Major Projects for Major New Drugs Innovation and Development[2018ZX09201005-009] ; Key Program for International Science and Technology Cooperation Projects of China[2016YFE0125100]
WOS关键词	METAL-ORGANIC FRAMEWORKS ; CARBON-DIOXIDE ; STABILITY ; BIOAVAILABILITY ; AMORPHIZATION ; INCLUSION ; BINDING
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
出版者	SPRINGER/PLENUM PUBLISHERS
WOS记录号	WOS:000470226300003
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/289596]
专题	中国科学院上海药物研究所
通讯作者	Wu, Li; Zhang, Suxia; Zhang, Jiwen
作者单位	1.Shanghai Inst Technol, Sch Chem & Environm Engn, Shanghai 201418, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Delivery Syst, Shanghai 201203, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Organ Chem, Shanghai 230032, Peoples R China 4.Hainan Hualon Pharmaceut Co Ltd, Haikou 570311, Hainan, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Wei,Guo, Tao,Wang, Caifen,et al. MOF Capacitates Cyclodextrin to Mega-Load Mode for High-Efficient Delivery of Valsartan[J]. PHARMACEUTICAL RESEARCH,2019,36(8):13.
APA	Zhang, Wei.,Guo, Tao.,Wang, Caifen.,He, Yuanzhi.,Zhang, Xi.,...&Zhang, Jiwen.(2019).MOF Capacitates Cyclodextrin to Mega-Load Mode for High-Efficient Delivery of Valsartan.PHARMACEUTICAL RESEARCH,36(8),13.
MLA	Zhang, Wei,et al."MOF Capacitates Cyclodextrin to Mega-Load Mode for High-Efficient Delivery of Valsartan".PHARMACEUTICAL RESEARCH 36.8(2019):13.