The effect of Si/Al ratio and drug loading level on the molecular behaviour and controlled release of 5-fluorouracil from zeolite H-Beta

G. A. Dunkley; S. L. McHugh; A. J. Porter; A. J. Wise; M. Appel; P. A. Cox; A. J. O’Malley

doi:10.1039/d5tb00256g

The effect of Si/Al ratio and drug loading level on the molecular behaviour and controlled release of 5-fluorouracil from zeolite H-Beta

G. A. Dunkley, S. L. McHugh, A. J. Porter, A. J. Wise, M. Appel, P. A. Cox, A. J. O’Malley

Research output: Contribution to journal › Article › peer-review

Abstract

The controlled release of anticancer drug 5-fluorouracil (5FU) from zeolite H-Beta has been studied with varying zeolite composition (Si/Al = 19 and 180), and correlated with its molecular behaviour, studied by quasielastic neutron scattering (QENS) and classical molecular dynamics simulations. The study aimed to understand the effect of increasing the Brønsted acid adsorption site concentration on the release properties of these potential drug delivery materials. A factor of ∼1.5 more 5FU was released from the sample with Si/Al = 180 over the release period, consistent with TGA analysis showing a factor of ∼1.5 more drug was encapsulated in this sample, which may initially seem counterintuitive given that it contains far fewer adsorption sites. Notably, the scale parameter of release from the H-Beta sample with Si/Al = 19 was slightly faster, despite the lower total loading and therefore final amount released from this sample. This slightly faster relative release rate was initially attributed to a lower level of steric ‘crowding’ between 5FU molecules in the H-Beta-19 pore system and thus hindrance to molecular mobility compared to H-Beta-180, consistent with the lower observed molecular loading level. QENS studies probing 5FU molecular motions observed the 5FU to be undergoing localised diffusion in the zeolite Beta intersections in both samples, with a higher proportion of mobile molecules performing this motion in H-Beta-19. This suggested the increased total drug loading in H-Beta-180, and resulting steric hindrance in the pore system, is the significant factor in adsorbed drug behaviour, and potentially the relative release rate from these zeolites. Molecular dynamics simulations probed the effect of increasing the drug loading level in the Beta framework and supported that increasing molecular loading significantly hindered total drug mobility due to favourable molecule-molecule interactions in the pore system. The study illustrates the complex relationship between zeolite composition, resulting drug loading level, molecular behaviour, and subsequent release profiles in the design of microporous controlled release systems for anticancer drug delivery.

Original language	English
Pages (from-to)	10314-10330
Number of pages	17
Journal	Journal of Materials Chemistry B
Volume	13
Issue number	33
Early online date	3 Jul 2025
DOIs	https://doi.org/10.1039/d5tb00256g
Publication status	Published - 20 Aug 2025

Data Availability Statement

Data for this article, including raw quasielastic neutron scattering data for the experiment 7-05-531, are available at the following DOI: https://doi.ill.fr/10.5291/ILL-DATA.7-05-531

Acknowledgements

This research made use of the Balena High Performance Computing (HPC) Service at the University of Bath, and Nimbus Cloud Supercomputer. The authors gratefully acknowledge the University of Bath's Research Computing Group80 for their support in this work. We would also like to thank Dr Gabriele Kociok-Kohn for running and maintenance of the PXRD instrument as well as Dr Remi Castaing for the running and maintenance of the TGA analyser as well as the whole of MC2 at the University of Bath. We acknowledge the Institut Laue-Langevin (ILL) neutrons for society facility in Grenoble, France, for their access to neutron beam facilities. The data from our experiment 7-05-531 can be found at the following DOI: https://doi.ill.fr/10.5291/ILL-DATA.7-05-531.

Funding

GAD is funded through the University of Bath URSA scheme. AJP acknowledges the UK Engineering and Physical Sciences Research Council (EPSRC) grant EP/R513155/1 for the University of Bath. SMCH acknowledges the Centre for Sustainable and Circular Technologies along with the UK Engineering and Physical Science Research Council (EPSRC) grant EP/LO16354/1 at the University of Bath. AJOM acknowledges Roger and Sue Whorrod for the funding of a Whorrod Fellowship, IChemE for the provision of the Syd Andrew Fellowship and the EPSRC Network Engineering Porous Materials at Multiple Scales (EP/X013065/1).

Funders	Funder number
Engineering and Physical Sciences Research Council	EP/R513155/1 , EP/LO16354/1 , EP/X013065/1

ASJC Scopus subject areas

General Medicine
General Chemistry
Biomedical Engineering
General Materials Science

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10.1039/d5tb00256gLicence: CC BY

Cite this

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title = "The effect of Si/Al ratio and drug loading level on the molecular behaviour and controlled release of 5-fluorouracil from zeolite H-Beta",

abstract = "The controlled release of anticancer drug 5-fluorouracil (5FU) from zeolite H-Beta has been studied with varying zeolite composition (Si/Al = 19 and 180), and correlated with its molecular behaviour, studied by quasielastic neutron scattering (QENS) and classical molecular dynamics simulations. The study aimed to understand the effect of increasing the Br{\o}nsted acid adsorption site concentration on the release properties of these potential drug delivery materials. A factor of ∼1.5 more 5FU was released from the sample with Si/Al = 180 over the release period, consistent with TGA analysis showing a factor of ∼1.5 more drug was encapsulated in this sample, which may initially seem counterintuitive given that it contains far fewer adsorption sites. Notably, the scale parameter of release from the H-Beta sample with Si/Al = 19 was slightly faster, despite the lower total loading and therefore final amount released from this sample. This slightly faster relative release rate was initially attributed to a lower level of steric {\textquoteleft}crowding{\textquoteright} between 5FU molecules in the H-Beta-19 pore system and thus hindrance to molecular mobility compared to H-Beta-180, consistent with the lower observed molecular loading level. QENS studies probing 5FU molecular motions observed the 5FU to be undergoing localised diffusion in the zeolite Beta intersections in both samples, with a higher proportion of mobile molecules performing this motion in H-Beta-19. This suggested the increased total drug loading in H-Beta-180, and resulting steric hindrance in the pore system, is the significant factor in adsorbed drug behaviour, and potentially the relative release rate from these zeolites. Molecular dynamics simulations probed the effect of increasing the drug loading level in the Beta framework and supported that increasing molecular loading significantly hindered total drug mobility due to favourable molecule-molecule interactions in the pore system. The study illustrates the complex relationship between zeolite composition, resulting drug loading level, molecular behaviour, and subsequent release profiles in the design of microporous controlled release systems for anticancer drug delivery.",

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AU - Porter, A. J.

AU - Wise, A. J.

AU - Appel, M.

AU - Cox, P. A.

AU - O’Malley, A. J.

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The effect of Si/Al ratio and drug loading level on the molecular behaviour and controlled release of 5-fluorouracil from zeolite H-Beta

Abstract

Data Availability Statement

Acknowledgements

Funding

ASJC Scopus subject areas

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EPSRC Network for Advanced Porous Materials at Multiple Scales (APoMM)

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The effect of Si/Al ratio and drug loading level on the molecular behaviour and controlled release of 5-fluorouracil from zeolite H-Beta

Abstract

Data Availability Statement

Acknowledgements

Funding

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Projects

EPSRC Network for Advanced Porous Materials at Multiple Scales (APoMM)

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