Drug-carrying "microparticles" developed by MIT engineers are capable of releasing two years’ worth of time-staggered vaccine doses with a single injection.
As many parents know, immunizing infants against childhood diseases takes many pinpricks and multiple doctor visits.
In developed countries like the US, those follow-up visits are an inconvenience that people sometimes skip or forget about. But in the developing world — where access to healthcare may be more limited — missed vaccinations can post a greater threat to individual and public health outcomes.
If infants miss required follow-ups, they face a higher disease risk. Around the world, an estimated 1.5 million children die each year from vaccine-preventable diseases (such as measles or pneumonia).
Now, 3D printing may help more babies receive the benefits of immunization without multiple doctor visits. Using a novel fabrication technique, MIT researchers have developed microparticles capable of delivering multiple, time-programmed doses of a drug in just a single injection.
The MIT research kicked off as part of a project funded by the Bill & Melinda Gates Foundation, which has made vaccine delivery one of its flagship global-health initiatives.
According to the Gates Foundation more than 70% of the world’s unvaccinated children live in 10 countries with large populations and “weak immunization systems.” To improve those systems, the Foundation sought a new, single-injection method for delivering all the vaccines a child needs during the first 1 – 2 years of life.
The vaccine delivery technique developed by MIT engineers (and detailed in a September 2017 study in the journal Science) is capable of doing just that.
The researchers’ innovation can create an entire library of tiny vaccine particles to be loaded into a single syringe. Each particle is sealed in PLGA, an FDA-approved form of polymer commonly used in sutures and prosthetics.
The polymer casings (which resemble coffee cups) for the microparticles are designed to degrade at specific times, subsequently releasing immunizing drugs into the body on a predictable schedule.
The team of engineers (led by senior study authors Robert Langer and Ana Jaklenec) had previous experience developing 3D-printed polymer particles capable of gradually releasing drugs into the body. But creating polymer cups capable of “spilling” their contents at precise intervals demanded a new fabrication technique — one capable of sealing many different microparticles inside many separate casings, each with a unique molecular weight.
The molecular weight and structure of the polymer casings determines the pace at which they degrade (and then release drugs) inside the body. To fabricate the tiny cups and seal them with uniquely weighted “lids,” the team invented a new 3D printing technique they dubbed SEAL, or “StampEd Assembly of polymer Layers.”
The SEAL method offers a high level of control over constructing 3-D microparticles for biomedical purposes. Similar to the way computer chips are manufactured, the researchers fabricate each “layer” of microparticles on its own, then assemble the layers together in a defined structure.
The researchers first created custom molds for the polymer cups and lids, and then use the molds to create and shape the PLGA encasings to their desired weights. Once the array of polymer cups was formed, the researchers used a custom-built, automated dispensing system to load each cup with the appropriate drug or vaccine.
After the cups are filled, the lids are deposited onto the cups and heated slightly – which allows a tight seal to form between the lid and cups. As aligned and lowered onto each cup, and the system is heated slightly until the cup and lid fuse together, sealing the drug inside.
In tests on mice for the study published in Science, the SEAL-sealed microparticles were effective at releasing vaccines in short, timed bursts (without prior leakage) at intervals between 9 and 41 days after injection. More importantly, the team’s immunization results with time-bursting microparticles were comparable to those seen with traditional multiple-dose methods.
“Part of the novelty is really in how we align and seal the layers,” said Ana Jaklenec. “This new method called SEAL can be used with any thermoplastic material and allows for fabrication of microstructures with complex geometries.”
The researchers say they’ve also developed particles capable of degrading and releasing drugs hundreds of days after injection — which could potentially revolutionize vaccine delivery.
Further study is necessary to ensure the drugs maintain stability while living in the blood (at body-heat temperatures) for such long periods, but the researchers are developing “stabilization” strategies as they test the SEAL approach with additional vaccines.
If further testing proves the particles can remain stable inside the body, this approach could be used to minimize injections for any drug demanding injections at regular intervals, such as allergy shots. Ultimately, greater use of the SEAL method could help more people receive drugs or vaccines — and stay well — with fewer visits to the doctor.
“The SEAL technique could provide a new platform that can create nearly any tiny, fillable object with nearly any material, which could provide unprecedented opportunities in manufacturing in medicine and other areas,” Jaklenec says.
The original research study “Fabrication of fillable microparticles and other complex 3D microstructures” was published in the Science in September 2017. Full information is available here.