When they get hot, they can be thrown in the bin: Some vaccines and other medicinal substances cost billions to refrigerate, and large quantities become unusable due to temperature fluctuations. Researchers are now presenting a possible solution to the problem: They have developed a hydrogel as a storage medium for active protein ingredients, which wraps around the substances like a protective coat and can therefore make them durable without refrigeration. For use, they can be easily released with a harmless solvent. The concept has the potential to curb losses and delivery problems, especially in the vaccine sector, the developers say.
Vaccines based on the effects of proteins or dead or harmless viruses have proven effective in protecting us from infectious diseases and curbing their spread and further development. One challenge, however, is getting the active ingredients from the manufacturers to the sometimes remote locations. As with other protein substances such as enzymes, the most problematic aspect is temperature. Because most of them have to be kept continuously below ten degrees Celsius in order to retain their effectiveness.
The corresponding cooling is associated with enormous costs: In 2020 it is estimated that 17.2 billion US dollars had to be spent on cold chains and a further significant increase is expected. Despite the effort, logistical problems lead to enormous losses: many active protein ingredients end up in the trash. Especially in countries with a weak infrastructure, cold chains often cannot be maintained uninterrupted and the valuable substances become unusable. Against this background, the research team led by Bruno Marco-Dufort from the Swiss Federal Institute of Technology in Zurich is developing alternative ways of protecting the active ingredients against temperature fluctuations.
Polymers keep proteins at bay
The concept they are now presenting is based on immobilization of the bioparticles so that they can no longer interact with one another when exposed to heat. Marco-Dufort explains the background: “You have to imagine the problem as with the protein of an egg: At room temperature or in the refrigerator, it retains its viscous protein structure. In boiling water or in a frying pan, however, this changes completely. The situation is similar with the proteins in a vaccine: as soon as they are exposed to certain temperatures, they clump together. This clumping cannot be reversed even if the vaccine is refrigerated again. After all, you can’t unboil an egg again,” says Marco-Dufort.
To prevent clumping, the scientists have developed a special formulation of a so-called hydrogel. A biocompatible polymer based on polyethylene glycol (PEG) ensures that the active ingredients are stabilized. It forms a kind of packaging that encapsulates proteins and keeps them separate from each other. This allows them to withstand significantly higher temperatures without losing their effectiveness: Instead of the traditional range of two to eight degrees Celsius, the hydrogel system allows proteins to withstand temperatures of up to 65 degrees Celsius, the researchers report.
Broad application potential
Releasing the encapsulated substances at the point of use is apparently also quite unproblematic: All that needs to be done is to add a harmless glucose solution to the hydrogel. The sugar molecules then react with components of the PEG network, thereby dissolving it. The researchers have already shown that the system works with different protein substances, including heat-sensitive enzymes and a protein-based vaccine. It was also shown that the system can thermally stabilize type 5 adenoviruses. These viruses are becoming increasingly important in vaccine development as carriers of genetic molecules. Recombinant adenovirus vectors have also been used in the fight against Covid-19.
According to the researchers, direct application of the system is already possible in the transport of heat-sensitive enzymes. The researchers say, however, that safety tests and clinical studies are still required before the method can be used in the vaccination sector. As they reiterate in conclusion, there could be a lot to gain from this: “The temperature sensitivity of vaccines represents a major hurdle for global campaigns, as vaccine distribution efforts and administrative costs outweigh production costs,” says Marco-Dufort. “If you want to improve the cold chain, however, enormous investments are required. Encapsulation, on the other hand, is a cost-saving solution, so the money can be used to produce more vaccine – which could save more lives.”
Source: Swiss Federal Institute of Technology in Zurich, specialist article: Science Advances, doi: 10.1126/sciadv.abo0502