Much of the Western world was introduced to the promise (and peril) of cold chains—supply chain networks that keep products cool or frozen during storage and shipping—during the rollout of COVID-19 vaccines, when suppliers struggled to deliver mRNA shots to those who needed them while keeping the jabs at their required sub-zero temperatures.
But cold chains also pose a hurdle for people around the globe to access other life-saving drugs and vaccines. Products like insulin, cancer drugs, and diagnostic enzymes need cold chains, too, and vast global disparities limit countries’ cooling infrastructure.
Luckily, a team of molecular engineers from ETH Zürich and Colorado-based startup Nanoly Bioscience have developed a new method of keeping drugs, enzymes, vaccines, and entire viruses stable without the need for a cold chain. Their technique stabilizes these products for weeks at a time with a hydrogel that can be switched off by adding a sugar. The method, detailed in a study published on Friday in Science Advances, could one day shake up the multibillion-dollar cold chain logistics industry.
“For many people around the world who need life-saving drugs, access is super complicated,” Eric Appel, a materials scientist at Stanford who was not involved in the study, told The Daily Beast. “It’s an important and complex challenge, and [these researchers] have a really elegant solution.”
Not all drugs require a cold chain for distribution—small molecules, like aspirin, can be stored and transported at room temperature without much trouble. But for larger compounds like proteins, heat can cause their precise, origami-like structures to unfold, degrade, or clump together. These changes can reduce both the safety and efficacy of a drug, Appel said.
“You could have the best active pharmaceutical ingredient in the world, but if it’s too unstable to put in a vial and ship anywhere, then it’s useless as a drug,” he said.
While cold chains stabilize drugs, vaccines, and enzymes by freezing the compounds in place, hydrogel research aims to reap the same benefits without the need for refrigerated trucks. Hydrogels are highly absorbent, but maintain a definite structure and do not dissolve in water—you probably use them already, since they’re the gel inside disposable diapers and the flexible material used to make most contact lenses.
““You could have the best active pharmaceutical ingredient in the world, but if it’s too unstable to put in a vial and ship anywhere, then it’s useless as a drug.””
— Eric Appel
In the new study, the scientists linked polyethylene glycol hydrogels together to form a molecular mesh, like a soccer net, that they said could entrap compounds like proteins and even entire viruses to prevent them from deforming or aggregating. They added the gel to solutions of large, temperature-dependent compounds including hemagluttanin (which is a key component of flu vaccines), topoisomerase I (used for cancer diagnosis), and lactase (the enzyme used to make lactose-free milk). In all cases, the gel kept the solutions potent, even after days and weeks of room temperature storage, while solutions without the gel degraded rapidly.
Appel said one of the beauties of a hydrogel is that it functions across the board based on size, and not any other characteristic specific to a compound.
“It could be a basketball, it could be a shovel, or a dining room table,” Appel said. “Anything that’s bigger gets stuck in the net.”
The drugs, enzymes, and other compounds are inert while trapped in the hydrogel, but the researchers designed an “on” switch. They showed that the net could be dissolved in as quickly as an hour by adding sugar.
Appel said future research to ready the technique for the clinic should focus on reducing the gel’s release time. Imagine a patient who sees a nurse for a vaccination: The health care worker pulls a vial off a shelf and adds a sugar solution to reactivate it.
“If you have to wait an hour before administering that vaccine, that’s a fairly long period of time,” he said.
Though the hydrogel-contained compounds were much better preserved than the ones left at room temperature without the gel, they did lose some of their efficacy over time—so it’s not perfect, Appel said. The hydrogel can’t prevent all of the ways the vaccines and drugs can break down chemically.
And don’t expect cold chains to go away anytime soon. The hydrogel used in the study still needs to be approved as safe by the Food and Drug Administration before it can start stabilizing drugs or vaccines. While preliminary data suggested that the gel components should be safe for human use, the authors warned that “one of the gel components could be found to be unsuitable for clinical translation.”
Even so, Appel said that he is “highly enthusiastic” about this approach, which could complement existing drug storage and transportation and preserve compounds for longer.
“Cold chains lead to so much waste, even here in the West,” he said. Hydrogel-based methods “could reduce costs, expand global access, and dramatically improve the stability of these kinds of drugs.”