Innovative Microparticles for Self-Boosting Vaccine Delivery and Stability

MIT researchers have developed innovative microparticles that enable “self-boosting” vaccines by releasing their payload at predetermined intervals, simplifying immunization with a single injection.

Engineering Controlled Vaccine Release

Vaccination typically requires multiple doses, from measles to Covid-19, before achieving full immunity. To simplify this process, researchers at MIT have developed innovative microparticles that can be engineered to release their vaccine payload at predetermined intervals, paving the way for “self-boosting” vaccines.

In a recent study, the team explored how these particles degrade over time and how they can be customized to deliver their contents at specific times. The research also provides valuable insights into preserving the stability of these contents until their release.

These particles, resembling small sealed cups, enable the design of vaccines that require just a single administration followed by automatic boosting at a later time. Once under the skin, the particles remain intact until it’s time for the vaccine to be released, subsequently breaking down similarly to absorbable sutures.

This innovative delivery method is particularly beneficial for administering childhood vaccinations in areas with limited access to healthcare services, according to the researchers.

Versatility Across Vaccine Types

“This technology can be broadly applied across various vaccine types, including recombinant protein-based, DNA-based, and RNA-based vaccines,” stated Ana Jaklenec, a research scientist at MIT’s Koch Institute. “Understanding the release mechanisms we’ve detailed in this study has enabled us to develop formulations that combat potential instability over time.”

Additionally, this delivery system holds promise for a variety of other therapeutic applications, such as cancer treatments, hormone therapies, and biologic drugs.

“Understanding the precise release mechanisms enables us to improve drug and vaccine stability while optimizing their timing.”

Microfabrication and Particle Design

Jaklenec and Robert Langer, a prominent figure at MIT’s Koch Institute, co-authored the study published in Science Advances. Morteza Sarmadi, a research specialist and recent MIT PhD graduate, is the lead author of the paper.

The team initially introduced their novel microfabrication technique for creating these hollow microparticles in a 2017 publication. These particles are composed of PLGA, a biocompatible polymer approved for use in medical devices like implants and sutures.

To fabricate the cup-shaped particles, researchers employ silicon molds to shape PLGA into cups and lids. After forming these cups, a specialized automated system fills them with drugs or vaccines. The lids are then aligned and heated to seal the contents securely inside.

This method, known as SEAL (StampEd Assembly of polymer Layers), is versatile enough to create particles of various shapes and sizes. A recent study in the journal Small Methods demonstrated an improved version of this technique for large-scale production.

Degradation Mechanisms and Stability Insights

In their latest research, the team aimed to gain further insights into how these particles degrade over time and what triggers them to release their contents. They also sought ways to enhance the stability of the drugs or vaccines contained within.

“We aimed to understand the mechanisms involved and leverage this information to improve drug and vaccine stability while optimizing their release kinetics,” Jaklenec explained.

Their investigations revealed that PLGA polymers gradually break down when exposed to water. Once enough polymers have decomposed, the lid becomes porous. Shortly after these pores form, the lid disintegrates, releasing the payload.

“We discovered that sudden pore formation prior to release is critical for this pulsatile delivery,” Sarmadi noted. “There are no pores for an extended period until there’s a significant increase in porosity just before release.”

The researchers explored various design parameters, such as particle size and polymer composition, to determine their effects on drug release timing. Surprisingly, they found that particle size and shape had minimal influence on release kinetics.

“The timing of release is primarily dictated by differences in polymer composition rather than size,” Sarmadi clarified. “For specific applications, we can select the appropriate polymer to achieve desired release intervals.”

Moreover, the team examined how environmental pH changes influence particle behavior. As PLGA polymers degrade, they produce lactic acid and glycolic acid, which can create an acidic environment harmful to sensitive proteins or nucleic acids within the particles.

In ongoing research, efforts are underway to mitigate this acidity increase to enhance payload stability.

Applications and Future Directions

Additionally, the team has developed a computational model that considers various design parameters to predict particle degradation within the body. This model could aid in developing not only PLGA particles but also other microfabricated or 3D-printed medical devices.

The researchers have applied this strategy to create a self-boosting polio vaccine currently undergoing animal testing. Typically, the polio vaccine requires two to four separate doses.

“We believe these core-shell particles have the potential to develop a safe single-injection self-boosting vaccine using a combination of particles with different release profiles,” Langer remarked. “This approach may enhance patient compliance and improve immune responses to vaccination.”

This advanced drug delivery technique could also prove beneficial in treating diseases like cancer. In a previous study published in Science Translational Medicine, the researchers demonstrated their ability to deliver drugs that stimulate immune responses in tumor environments through several mouse models.

Funding for this research was provided by the Bill and Melinda Gates Foundation.