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JACS_BES_10Oct19.pdf (6.73 MB)
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Elucidating the Drug Release from Metal-Organic Framework Nanocomposites via in Situ Synchrotron Microspectroscopy and Theoretical Modelling

preprint
submitted on 13.10.2019 and posted on 16.10.2019 by Barbara Souza, Lorenzo Dona, Kirill Titov, Paolo Bruzzese, Zhixin Zeng, Yang Zhang, Arun Babal, Annika Moslein, Mark Frogley, Magda Wolna, Gianfelice Cinque, Bartolomeo Civalleri, Jin-Chong Tan
Nanocomposites comprising metal-organic frameworks (MOFs) embedded in a polymeric matrix are promising carriers for drug delivery applications. While understanding the chemical and physical transformations of MOFs during the release of confined drug molecules is challenging, this is central to devising better ways for controlled release of therapeutic agents. Herein we demonstrate the efficacy of synchrotron microspectroscopy to track the in situ release of 5-fluorouracil (5-FU) anticancer drug molecules from a drug@MOF/polymer composite (5-FU@HKUST-1/polyurethane). Using experimental time-resolved infrared spectra jointly with newly developed density functional theory calculations, we reveal the detailed dynamics of vibrational motions underpinning the dissociation of 5-FU bound to the framework of HKUST-1 upon water exposure. We discover that HKUST-1 creates hydrophilic channels within the hydrophobic polyurethane matrix hence helping to tune drug release rate. The synergy between a hydrophilic MOF with a hydrophobic polymer can be harnessed to engineer a tunable nanocomposite that alleviates the unwanted burst effect commonly encountered in drug delivery.

Funding

ERC Consolidator Grant 771575 (PROMOFS)

Minas Gerais Research Foundation (FAPEMIG CNP) n21.949.888/0001-83

History

Email Address of Submitting Author

jin-chong.tan@eng.ox.ac.uk

Institution

University of Oxford

Country

United Kingdom

ORCID For Submitting Author

0000-0002-5770-408X

Declaration of Conflict of Interest

No conflict of interest

Version Notes

Submitted to JACS for review

Exports