Stanford researchers have developed an injectable gel that improves the delivery of medications into the body, according to a paper published in “Nature” in February. They believe this gel could be used to improve COVID-19 vaccines, due to its temperature-resistant and slow-releasing properties.
The research was led by Eric Appel, assistant professor of material science and engineering, who began developing the gel when he was a postdoctoral student several years ago. The Appel lab focuses on optimizing the delivery of medications, such as insulin, vaccines and cancer therapies.
“We like to identify the real-world limitations of medications and then use our knowledge of material science to improve that delivery,” said Emily Gale Ph.D. ’21. During this pandemic, the researchers became particularly curious about how the gel might be used to deliver COVID-19 vaccines more effectively.
A crucial property of this gel is its ability to withstand changes in structure when exposed to increases in temperature. In most gels that are used for drug delivery, the gel melts into a liquid as soon as it is exposed to temperature of the body.
“When you raise the temperature of a gel, this typically causes the molecules to move apart from one another,” said Huada Lian M.S. ’18 Ph.D. ’21, who conducted simulations exposing the atoms of the gel to various temperatures.
In other words, an increase in temperature can disrupt the interactions between the molecules that make up the gel, which causes the gel to dissolve. When the gel dissolves, it releases the medication all at once instead of at a slower interval. “We want the gel to stay a solid ‘blob’ under the skin so that it can release the vaccine slowly,” Gale explained.
The gel developed by Appel and his colleagues is resistant to changes in temperature and retains its solid state at the body temperatures of injected mice.
“When we increased the temperature of our gel, we found that it did not disintegrate,” Lian said. “In fact, we found that the interactions between molecules in the gel actually grew stronger as the temperature rose.”
Gale explained that the body’s immune response is heightened when the vaccine is released over a long period of time. This is because this slow-release process mimics what actually happens when a person is infected with a disease. She said this enhanced immune response could potentially replace the need for COVID-19 booster shots, which would be particularly valuable for communities where access to healthcare services is restricted.
The temperature-resistant property of the gel also helps it to protect components of the vaccine from being damaged in warm environments. The Pfizer and Moderna vaccines must be stored at cool temperatures to prevent the SARS-CoV-2 mRNA and proteins from being destroyed.
In their research, Gale and her colleagues found that the gel helped to stabilize the SARS-CoV-2 proteins at high temperatures, protecting them from destruction. She said that the gel could be added to vaccines that need to be delivered in hot climates or in regions without medical-grade freezers, which could remove some barriers to vaccination globally.
In addition to being temperature-resistant, the gel also exhibits properties called “shear thinning” and “self-healing.” Shear thinning is what occurs when the gel passes through the needle of the vaccine syringe.
“The gel is solid-like in the syringe, but when you apply pressure by pushing on the plunger, it undergoes shear thinning, which allows it to act like a liquid briefly under pressure,” Gale said.
This transformation increases the ease of injection. However, as soon as the gel is pushed out of the needle and into the patient’s body, it needs to become solid again in order to release the vaccine slowly. This is a process that Gale referred to as “self-healing,” which means that, in the absence of the pressurized environment of the needle, the gel returns to its solid state.
Appel believes that the gel’s properties could have broader implications for combatting other diseases as well. He said it could show promise in vaccinations against influenza, HIV, malaria and other conditions that would benefit from this slow-release technology.
“We are trying to make a gel that you could inject with a pin, and then you’d have a little blob that would dissolve away very slowly for three to six months to provide continuous therapy,” Appel told Stanford News. “This would be a game-changer for fighting critical diseases around the world.”