Sep 18, 2017 | By Benedict

Engineers at MIT have developed a 3D printing method that could allow doctors to deliver several drug or vaccine doses over a period of time with just a single injection. The "SEAL" technique works by 3D printing cup-like microparticles that can store and seal the drug doses.

For those who fear injections, the idea of drinking your next vaccine from a coffee cup may sound quite appealing. Two cappuccinos and a polio shot, please.

Unfortunately, a group of MIT engineers have just developed a more metaphorical than literal form of “coffee cup” drug dispensing. Far too small to hold in your fingers, their tiny 3D printed cups—which are actually microparticles—can be filled with various drugs or vaccines, sealed with a lid, and then injected into the body.

And they’re not made from china, either. These 3D printed cups are made from a biocompatible, FDA-approved polymer which can be programmed to degrade at specific times. This allows certain parts of the cocktail to be released at specific times, meaning patients receiving the drugs or vaccines only need one jab to receive several doses.

“We are very excited about this work,” said Robert Langer, the David H. Koch Institute Professor at MIT. “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.”

Funded by a grant from the Bill and Melinda Gates Foundation, the MIT researchers’ project was started in order to find a way of delivering multiple doses of a vaccine over a specified period of time. This was deemed particularly important for vaccinations in countries where patients are often unable or unlikely to return for follow-up injections.

Langer explained that the 3D printing technique “could have a significant impact on patients everywhere, especially in the developing world where patient compliance is particularly poor.” Babies would potentially be able to receive a single shot that would cover their required vaccines for the first one to two years of their life.

The project is particularly interesting because its 3D printed “cups” aim to deliver short bursts of their contents at very specific times, withholding their contents during the interim periods. This is different to other delivery systems that either deliver all their contents at once, or release a continuous, gradual amount over time.

But making a drug delivery system that can deliver its contents at precise intervals requires the right materials. In this case, the researchers decided to use PLGA, a biocompatible polymer that has been approved for use in medical devices and which can be made to degrade at specific times. The only problem was fabrication: conventional 3D printing systems weren’t able to print the PLGA cups exactly how the researchers wanted them.

The new technique developed by the researchers is inspired by computer chip manufacturing. The team used photolithography to make silicon molds for the cups and the lids, fitting around 2,000 of the molds onto a glass slide and using them to shape the PLGA cups and lids. Then, when the polymer cups were ready, an automated dispensing system was used to fill them up with the necessary drugs. Lids are then lowered on to the cups and fused on with heat.

“We developed a new method that can make structures which current 3D printing methods cannot,” said Ana Jaklenec, a research scientist at MIT’s Koch Institute for Integrative Cancer Research. “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 3D microfluidic devices.”

By adjusting the molecular weight and structure of the polymer, the researchers can adjust how fast the particles will degrade after injection, which in turn determines when the drugs will be released. Does it work? You bet it does. The team tried the approach out on mice, finding that particles could release in sharp bursts, without leaking, at 9, 20, and 41 days after injection. Moreover, the researchers found that by filling their “coffee cups” with a delicious brew of ovalbumin (a protein found in egg whites that is commonly used to experimentally stimulate an immune response), they could induce the effect of two separate injections with just one—even with half the dosage.

The MIT researchers have even tried 3D printing microparticles that can release drugs after hundreds of days. In these cases, however, the researchers must ensure that the drug or vaccine remains stable at body temperature.

The technique is currently being tested with a variety of drugs, while Langer, Jaklenec, and the rest of their team are also exploring strategies to stabilize the vaccines.

“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,” Langer said.

The researchers’ study, “Fabrication of fillable microparticles and other complex 3D microstructures,” has been published in Science. Its lead authors are postdoc Kevin McHugh and former postdoc Thanh D. Nguyen.

Posted in 3D Printing Application

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