Pharmaceutical Research

, 36:117 | Cite as

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

  • Wei Zhang
  • Tao Guo
  • Caifen Wang
  • Yuanzhi He
  • Xi Zhang
  • Guangyu Li
  • Yizhi Chen
  • Jun Li
  • Yangjing Lin
  • Xu Xu
  • Li WuEmail author
  • Suxia ZhangEmail author
  • Jiwen ZhangEmail author
Research Paper



To investigate the mechanism of enhancing solubility and bioavailability of water-insoluble drug, valsartan (VAL), with being mega-loaded by cyclodextrin metal organic framework (CD-MOF).


VAL 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) 13C solid-state nuclear magnetic resonance spectroscopy ( 13C 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.


As a carrier with payload 150% higher than conventional CD complexation, CD-MOF included molecules of VAL as complexations in the chambers of (γ-CD)2, and nanoclusters in the confined spherical cages of (γ-CD)6 confirmed by SAXS and 13C 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 (γ-CD)6 are critical in dramatically improving the apparent solubility (39.5-fold) and oral bioavailability (1.9-fold) of VAL in contrast to γ-CD inclusion.


The new understanding of drug nanoclusters in CD-MOF will help to design more efficient drug delivery systems using CD-MOF carrier with nanocavities.

Key Words

Bioavailability cyclodextrin metal-organic framework solubility valsartan 



13C solid-state nuclear magnetic resonance spectroscopy




Cyclodextrin metal-organic frameworks


Differential scanning calorimetry


Powder X-ray diffraction


Small-angle X-ray scattering


Scanning electron microscopy


Synchrotron radiation-based Fourier transform-infrared spectroscopy




Valsartan cyclodextrin inclusion complex


Valsartan loaded by cyclodextrin metal-organic frameworks


Supplementary material

11095_2019_2650_MOESM1_ESM.docx (534 kb)
ESM 1 (DOCX 534 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.School of Chemical and Environmental EngineeringShanghai Institute of TechnologyShanghaiChina
  2. 2.Center for Drug Delivery Systems Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghaiChina
  3. 3.Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghaiChina
  4. 4.Hainan Hualon Pharmaceutical Co., LtdHaikouChina

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