Compact microparticles offer new vaccine delivery approach
Researchers from Massachusetts Institute of Technology (MIT) have come up with single-shot, “self-boosting” vaccines made from a biocompatible polymer (PLGA). The polymer microparticles containing the vaccines resemble tiny coffee cups sealed with a lid. The particles can remain under the skin until the vaccine is released and only then breaks down completely.
The material has already been used in medical implants and prosthetic devices, but this time, the unique cup-shape of the particles was created with silicon molds before an automated dispensing system filled each cup with a drug or vaccine. The cups are each fused with a lid to seal the drug inside, just like a Starbucks order.
The technique is called SEAL (StampEd Assembly of polymer Layers) – it can be used to produce particles of any shape or size. It could also be used to deliver a range of other therapeutics, including cancer drugs, hormone therapy, and biologic drugs.
“This is a platform that can be broadly applicable to all types of vaccines, including recombinant protein-based vaccines, DNA-based vaccines, even RNA-based vaccines,” said Ana Jaklenec, a research scientist at MIT’s Koch Institute for Integrative Cancer Research. “We wanted to understand [the process of how the vaccines are released], and how that information can be used to help stabilise drugs and vaccines and optimise their kinetics.”
Their studies of the release mechanism revealed that the PLGA polymers that make up the particles are gradually cleaved by water, and when enough of these polymers have broken down, the lid becomes very porous. Very soon after these pores appear, the lid breaks apart, spilling out the contents.
The researchers then analysed a variety of design parameters, including how the size and shape of the particles and the composition of the polymers used to make them affected the timing of drug release.
To their surprise, the researchers found that particle size and shape had little effect on drug release kinetics. This sets the particles apart from most other types of drug delivery particles, whose size plays a significant role in the timing of drug release. Instead, the PLGA particles release their payload at different times based on differences in the composition of the polymer and the chemical groups attached the ends of the polymers.
To help improve the stability of the payload carried within the particles, the researchers also developed a computational model that assesses different design parameters and reliably predicts how a particular particle will degrade in the body.
A self-boosting polio vaccine has been designed using this strategy and is now being tested in animals. Usually, the polio vaccine has to be given as a series of two to four separate injections – a full course of the injections is necessary for the vaccine to be effective.
“We believe these core shell particles have the potential to create a safe, single-injection, self-boosting vaccine in which a cocktail of particles with different release times can be created by changing the composition,” said Robert Langer, the David H. Koch Institute Professor at MIT. “Such a single injection approach has the potential to not only improve patient compliance but also increase cellular and humoral immune responses to the vaccine.”
This type of vaccine delivery could be particularly useful for administering childhood vaccinations in regions where people don’t have frequent access to medical care.
