A new storage technique can keep protein-based drugs and vaccines stable without keeping them cold. The discovery, led by researchers at Penn State, could eliminate the need for refrigeration for hundreds of life-saving medicines like insulin, monoclonal antibodies and viral vaccines.
"Over 80% of biologic drugs and 90% of vaccines require temperature-controlled conditions. This approach could revolutionize their storage and distribution, making them more accessible and affordable for everyone," said Scott Medina, study lead and William and Wendy Korb Early Career Professor of Biomedical Engineering at Penn State. "This would save billions of dollars currently spent on keeping these products cold throughout the supply chain and potentially enable the use of protein therapies in environments where constant refrigeration is not possible."
The research was recently published in the journal Nature Communications. Through a series of experiments, the research team replaced the water-based solution commonly used in protein-based medications with a perfluorocarbon oil and tested five different proteins with a range of health-related functions such as antibodies and enzymes.
When tested in mice, the researchers found the new solution was just as effective as the refrigerated versions and showed no signs of toxicity, meaning there were no adverse health effects from the oil-based solution.
The researchers also found that the oil-based solution was naturally sterile for the protein samples, noting that they could not be contaminated by bacteria, fungi or viruses which require a water-based environment to grow and survive.
There was one problem: proteins in water-based environments spread themselves evenly throughout the liquid. In oil, they're not so soluble, Medina explained. So, the team developed a surfactant - a molecule that coats the surface of the protein - to shield the surface of the protein in a way that would allow it to evenly disperse itself throughout the solution.
The surfactant also created a protective shell around the protein, keeping it stable and preventing it from breaking down even at temperatures up to 212 degrees Fahrenheit, which would normally cause water to boil.
"Think of it like raincoats for proteins," said Medina, who is also affiliated with Penn State's Huck Institutes of the Life Sciences. "Just like a raincoat keeps you dry, this protective shell keeps the protein safe from heat and contamination, allowing it to stay stable and functional."
Protein-based drugs and vaccines are typically sensitive to heat, light and movement, all of which can cause them to lose their structure and function over time, Medina explained. Refrigeration helps to slow down that degradation process, so the medication will remain effective until it is administered.
"At high temperatures, proteins will start to unfold and become inactive," Medina said. "The unfolding happens because when the temperature increases, the energy of the water molecules will pull the protein apart and unfold it. Because of this, protein therapies often have to be stored in fridges or freezers to prevent the unfolding from happening."
Medina said these findings have the potential to limit or eliminate cold chain logistics, which is the supply network necessary for getting the therapies from where it is being produced to the various distribution centers prior to being administered to the patients.
In 2020, another team of researchers found that cold chain logistics are projected to cost $58 billion globally by 2026.
"If something goes wrong in the process, the activity of the protein therapy could be lost, the drug could no longer be effective or it becomes contaminated and the patients could potentially be harmed," Medina said.
The researchers said their approach has the potential to reduce costs and barriers for pharmaceutical companies, which could lead to more savings and better access for the patients in need of these therapies.
"This new method could also lower barriers and allow the drugs to be distributed in resource-scare environments across all populations," Medina said. "We could even use this for those on the battlefield, where these therapies would be needed but access to refrigeration is limited."
In the future, the researchers aim to demonstrate that their method works with additional proteins and partner with pharmaceutical companies to stabilize protein molecules or peptides that could be used in a range of medications.
"We are currently in the process of securing patent rights and hope to partner with pharmaceutical companies to make their protein products more stable and accessible," Medina said.
The team includes Girish Kirimanjeswara, associate professor of veterinary and biomedical science; Atip Lawanprasert, Mariangely González Vargas and Arishya Dewan, Penn State graduate students; as well as Harminder Singh, postdoctoral scholar; and Sopida Pimcharoen, undergraduate student. The Defense Advanced Research Projects Agency funded this work.
