17-05-2025
Scared of injections? Polymer microparticles put an end to multiple vaccine jabs
Scientists in the U.S. have developed polymer microparticles that can release vaccines at specific times after injection, sometimes even months later, potentially removing the need for multiple separate shots.
In an effort to improve immunization rates among the 20 percent of children who remain unprotected worldwide, the Massachusetts Institute of Technology (MIT) developed a method that allows multiple vaccine doses to be delivered from a single injection, with each dose released at different intervals.
The groundbreaking solution, created under the leadership of Ana Jaklenec, PhD, and Robert Langer, PhD, of MIT's Koch Institute, could help prevent 1.5 million child deaths each year from diseases that could be avoided with proper vaccination.
As per the study, these particles were able to deliver two doses of the diphtheria vaccine, one immediately and the other after two weeks, with tests on mice showing antibody levels comparable to those in mice that received two separate injections spaced two weeks apart.
Now aiming to extend the release intervals, the team believes these particles could be ideal for delivering childhood vaccines that require multiple doses over several months, such as the polio vaccine.
Back in 2018, the team proved that vaccine delivery PLGA-based particles could release two doses of the polio vaccine 25 days apart. However, one of PLGA's drawbacks was that as the particles gradually degrade inside the body, they can generate an acidic environment that can potentially degrade the vaccine they carry.
Led by Linzixuan (Rhoda) Zhang, PhD, a chemical engineering graduate from MIT, the research focused on overcoming this issue while exploring a biodegradable, hydrophobic polymer, known as polyanhydride, which has the potential to better protect the vaccine.
According to the researchers, polyanhydrides gradually break down inside the body, but unlike other materials, their byproducts barely dissolve in water. This results in a much more stable and less acidic environment.
This prompted the team to develop a library of 23 different polymers, which they then evaluated based on their ability to remain stable at temperatures of at least 104 degrees Fahrenheit. They additionally assessed whether the polymers could remain stable throughout the process required to form them into microparticles.
For the particles, the team developed a process called stamped assembly of polymer layers, or SEAL. They first used silicon molds to create cup-shaped particles filled with the vaccine antigen, then sealed them with a heat-applied polymer cap. Polymers that were too brittle or failed to seal properly were excluded, leaving six top candidates.
Using these polymers, the scientists then made particles that delivered an immediate dose of the diphtheria vaccine to mice, followed by a second one two weeks later. And they were stunned when, four weeks later, the mice developed antibody levels nearly identical to those given two separate injections two weeks apart.
For the study, the team also developed a machine learning model to investigate the key factors that influence how quickly the particles degrade inside the body. These included the type of monomers that go into the material, the monomers' ratio, the polymer's molecular weight, and the loading capacity or how much vaccine can go into the particle.
The model helped them quickly evaluate nearly 500 possible particles and predict their release timelines. By testing several of these in controlled buffer solutions, they confirmed that the model's predictions were accurate.
"If we want to extend this to longer time points, let's say over a month or even further, we definitely have some ways to do this, such as increasing the molecular weight or the hydrophobicity of the polymer," Zhang highlighted. "We can also potentially do some cross-linking."
According to Zhang, these further modifications to the polymer's chemistry could slow down the release kinetics or extend the particle's retention time in the body.
The team now hopes to assess the potential of these delivery particles for other vaccine types. They could also prove useful for delivering other types of drugs that are sensitive to acidity and need to be given in multiple doses, they say.
"This technology has broad potential for single-injection vaccines, but it could also be adapted to deliver small molecules or other biologics that require durability or multiple doses," Jaklenec concludes in a press release. "Additionally, it can accommodate drugs with pH sensitivities."
The research has been published in the journal Advanced Materials.
