No one likes getting shots, and young children like getting shots least of all. Unfortunately, young children are typically the ones who need to get the most shots in the shortest period of time as they build up their immunity. Experts have talked about the possibility of making life easier for people who take multiple medications by combining them all in one 3D printed pill, so wouldn’t it be great if they could do the same thing with vaccines? If every vaccine a child needed could be combined into one shot, then they would only need to make one trip to the doctor and be done with it. As it turns out, that’s a possibility – and 3D printing has a role to play in that, too.
Engineers at MIT have used 3D printing to create a microparticle that is made from a biocompatible, FDA-approved polymer and resembles a tiny cup. These cups can be filled with doses of drugs or vaccines and sealed with a lid, then injected into a patient. The cups then biodegrade at predetermined rates, releasing the drugs or vaccines into the patient’s system on a specific schedule.
“We are very excited about this work because, for the first time, we can create a library of tiny, encased vaccine particles, each programmed to release at a precise, predictable time, so that people could potentially receive a single injection that, in effect, would have multiple boosters already built into it,” said Robert Langer, the David H. Koch Professor at MIT. “This could have a significant impact on patients everywhere, especially in the developing world where patient compliance is particularly poor.”
Langer and his lab began researching vaccine delivery alternatives as part of a project funded by the Bill & Melinda Gates Foundation. The foundation wanted to find a way for a single injection to deliver multiple vaccine doses over a period of time, in particular so that babies in developing countries, who don’t always have access to doctors, could receive all the immunizations they needed for their first couple years of life in one shot.
Langer has previously developed polymer particles with drugs embedded throughout them, for slow release over time. For this project, however, the goal was to deliver short bursts of a vaccine at specific times. They began working with PLGA, a biocompatible polymer approved for use in medical devices like implants, sutures and prosthetics. The material can be designed to degrade at different rates, so that multiple tiny cups could be created to release their contents at different times. The rate of degradation is determined by the molecular weight of the PLGA and the structure of the polymer molecules’ “backbone.”
Conventional 3D printing didn’t work for the size and material, so the researchers created a new method. They used photolithography to create silicone molds for both the cups and the lids, then placed about 2,000 of the molds onto a glass slide. The molds were then filled with PLGA, in the shape of cubes with edges only a few hundred microns long. They then built a special, automated dispensing system that filled each cube with a dose of vaccine or medicine, then placed lids on them. The cups were then heated until they fused with the lids and fully sealed.
“Each layer is first fabricated on its own, and then they’re assembled together,” said Ana Jaklenec, a research scientist at MIT’s Koch Institute for Integrative Cancer Research. “Part of the novelty is really in how we align and seal the layers. In doing so we developed a new method that can make structures which current 3-D printing methods cannot. This new method called SEAL (StampEd Assembly of polymer Layers) can be used with any thermoplastic material and allows for fabrication of microstructures with complex geometries that could have broad applications, including injectable pulsatile drug delivery, pH sensors, and 3-D microfluidic devices.”
The particles were tested on mice, and the researchers found that they released their contents at 9, 20 and 41 days after injection. None of them leaked before they were scheduled to release. They also tried filling the particles with ovalbumin, a protein found in egg whites that is often used to experimentally stimulate an immune response. They injected a shot with particles containing ovalbumin designed to release at 9 days, and particles designed to release at 41 days. The immune response that was stimulated was comparable to that produced by two conventional injections with double the dose.
Some of the particles can also degrade hundreds of days after the injection. According to the researchers, the challenge in developing long-term vaccinations using this method is keeping the drug or vaccine stable at body temperature for a long enough time, but they are working on methods of stabilizing the vaccines. They’re also testing the method with a variety of drugs and vaccines, including existing ones like polio vaccine as well as some still in development.
“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,” said Langer.
The research was documented in a paper entitled “Fabrication of fillable microparticles and other complex 3D microstructures,” which you can read here. Authors of the study include Kevin J. McHugh, Thanh D. Nguyen, Allison R. Linehan, David Yang, Adam M. Behrens, Sviatlana Rose, Zachary L. Tochka, Stephany Y. Tzeng, James J. Norman, Aaron C. Anselmo, Xian Xu, Stephanie Tomasic, Matthew A. Taylor, Jennifer Lu, Rohiverth Guarecuco, Robert Langer and Ana Jaklenec.
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