Mechanical release of homogenous proteins from supramolecular gels

Simona Bianco, Muhammad Hasan, Ashfaq Ahmad, Sarah-Jane Richards, Bart Dietrich, Matthew Wallace, Qiao Tang, Andrew J. Smith, Matthew I. Gibson () and Dave J. Adams ()
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Simona Bianco: University of Glasgow
Muhammad Hasan: University of Warwick
Ashfaq Ahmad: University of Warwick
Sarah-Jane Richards: University of Warwick
Bart Dietrich: University of Glasgow
Matthew Wallace: University of East Anglia, Norwich Research Park
Qiao Tang: University of Warwick
Andrew J. Smith: Diamond House, Harwell Science and Innovation Campus
Matthew I. Gibson: University of Warwick
Dave J. Adams: University of Glasgow

Nature, 2024, vol. 631, issue 8021, 544-548

Abstract: 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 household1. 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 trehalose2, sucrose or polymers3 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–thaw4, leading to a very complex and expensive supply chain. Other ideas involve ensilication5 and chemical modification of proteins6. In short, protein stabilization is a challenge with no universal solution7,8. 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.

Date: 2024
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DOI: 10.1038/s41586-024-07580-0

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