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Bianco, Simona, Hasan, Muhammad, Ahmad, Ashfaq, Richards, Sarah-Jane, Dietrich, Bart, Wallace, Matthew 
ORCID: https://orcid.org/0000-0002-5751-1827, Tang, Qiao, Smith, Andrew J., Gibson, Matthew I. and Adams, Dave J.
(2024)
Mechanical release of homogenous proteins from supramolecular gels.
Nature, 631 (8021).
544–548.
ISSN 0028-0836
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Abstract
A long-standing challenge is how to formulate proteins and vaccines to retain function during storage and transport and to remove the burdens of cold-chain management. Any solution must be practical to use, with the protein being released or applied using clinically relevant triggers. Advanced biologic therapies are distributed cold, using substantial energy, limiting equitable distribution in low-resource countries and placing responsibility on the user for correct storage and handling. Cold-chain management is the best solution at present for protein transport but requires substantial infrastructure and energy. For example, in research laboratories, a single freezer at −80 °C consumes as much energy per day as a small household 1. Of biological (protein or cell) therapies and all vaccines, 75% require cold-chain management; the cost of cold-chain management in clinical trials has increased by about 20% since 2015, reflecting this complexity. Bespoke formulations and excipients are now required, with trehalose 2, sucrose or polymers 3 widely used, which stabilize proteins by replacing surface water molecules and thereby make denaturation thermodynamically less likely; this has enabled both freeze-dried proteins and frozen proteins. For example, the human papilloma virus vaccine requires aluminium salt adjuvants to function, but these render it unstable against freeze–thaw 4, leading to a very complex and expensive supply chain. Other ideas involve ensilication 5 and chemical modification of proteins 6. In short, protein stabilization is a challenge with no universal solution 7,8. Here we designed a stiff hydrogel that stabilizes proteins against thermal denaturation even at 50 °C, and that can, unlike present technologies, deliver pure, excipient-free protein by mechanically releasing it from a syringe. Macromolecules can be loaded at up to 10 wt% without affecting the mechanism of release. This unique stabilization and excipient-free release synergy offers a practical, scalable and versatile solution to enable the low-cost, cold-chain-free and equitable delivery of therapies worldwide.
| Item Type: | Article |
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| Additional Information: | Data availability statement: All data are available in the main text or the Supplementary Information or available on reasonable request. Funding information: This work has been supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 814236, European Research council grant no. 866056, Royal Society for an Industry Fellowship (M.I.G.) 191037, Engineering and Physical Sciences Research Council (EP/L021978/2) and the University of Glasgow. M.W. thanks UKRI for a Future Leaders Fellowship (MR/T044020/1). This work was carried out with the support of Diamond Light Source, instrument I22 (proposal SM27906). We thank N. Cowieson (Diamond Light Source) for help collecting the SAXS data at B21 (SM37100). This work benefitted from the SasView software, originally developed by the DANSE project under NSF award DMR-0520547. We would like to thank J. R. Bame and G. J. Anderson (University of Strathclyde) for collecting the high-resolution mass spectrometry data. For the purpose of open access, the author(s) has applied a Creative Commons Attribution (CC BY) license to any Author Accepted Manuscript version arising from this submission. |
| Uncontrolled Keywords: | general,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/1000 |
| Faculty \ School: | Faculty of Science > School of Pharmacy (former - to 2024) |
| UEA Research Groups: | Faculty of Science > Research Groups > Pharmaceutical Materials and Soft Matter |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 25 Jul 2024 13:30 |
| Last Modified: | 25 Sep 2024 17:50 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/96026 |
| DOI: | 10.1038/s41586-024-07580-0 |
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