Scientists have designed a new type of hydrogel that enables biologics such as antibodies, enzymes, and protein-based vaccines to withstand a greater range of temperature fluctuations without losing their functionality. This hydrogel may offer a new way to store and transport biologics, reducing costs and health risks associated with the cold chain.

“[In] 2020, the overall market for cold chain services was $17.2 billion and forecasted to rise to $21.3 billion by 2024,” wrote the scientists in their report of the work, which was published in Science Advances (“Thermal stabilization of diverse biologics using reversible hydrogels”). Mark Tibbitt, PhD, an assistant professor in the Molecular Engineering Laboratory at ETH Zurich, led the work.

Most biologics require strict temperature regulation from the manufacturing line to injection into a human arm. Maintaining a constant temperature along the cold chain is a challenging feat in the best of circumstances. In Sub-Saharan Africa and other developing regions, for example, limited transport infrastructure and unreliable electricity compound the already immense challenges of delivering viable products.

“Think of it like an egg,” explained Bruno Marco-Dufort, a doctoral researcher in Tibbitt’s lab, in referring to a protein-based biologic. “At room temperature or in the refrigerator the egg maintains its viscous-like protein structure, but once it hits boiling water or the frying pan its structure changes permanently.”

To overcome this challenge, Tibbit’s team, in conjunction with others from ETH Zurich and entrepreneurs from Colorado-based Nanoly Bioscience, developed a new type of hydrogel that can encapsulate the proteins and enable them to withstand a greater range of temperature fluctuations.

“Our approach was based on the use of dynamic covalent boronic ester–based cross-links, which readily form under physiological conditions,” they wrote. “Boronic ester–based hydrogels have been used as responsive drug delivery systems, as dynamic cell culture scaffolds, and as sugar-sensing materials.”

The team tested these hydrogels on a range of biologics—clinical diagnostic enzymes, protein-based vaccines, and even whole viruses—and were successful in thermally stabilizing them by encapsulation. “Protection was attributed to the formation of polymer networks around the biologics, which restricted their mobility and physically prevented them from interacting with each other, reducing aggregation and bioactivity loss after exposure to heat,” they wrote.

Instead of the traditional 2 to 8 °C (35 to 45 °F) range for the cold chain, encapsulation allows for a range of 25 to 65 °C (75 to 150 °F). Most importantly, the encapsulated cargo can simply be released by adding a sugar solution, enabling easy on-demand recovery at the point of use.

Furthermore, preliminary toxicology data showed that the gel components are safe for in vivo use.

More research, safety studies, and clinical trials need to be conducted before the hydrogels can be implemented for widespread distribution of biologics. But they are a step in the right direction. Their more immediate use is for transporting heat-sensitive enzymes or protein molecules used in research settings.

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