Microparticles created by new 3D fabrication method could release drugs or vaccines long after injection.
MIT engineers have invented a new 3-D fabrication method that can generate a novel type of drug-carrying particle that could allow multiple doses of a drug or vaccine to be delivered over an extended time period with just one injection.
The new microparticles resemble tiny coffee cups that can be filled with a drug or vaccine and then sealed with a lid. The particles are made of a biocompatible, FDA-approved polymer that can be designed to degrade at specific times, spilling out the contents of the “cup.”
“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. This could have a significant impact on patients everywhere, especially in the developing world where patient compliance is particularly poor,” says Robert Langer, the David H. Koch Institute Professor at MIT.
Langer and Ana Jaklenec, a research scientist at MIT’s Koch Institute for Integrative Cancer Research, are the senior authors of the paper, which appears online in Science on Sept. 14. The paper’s lead authors are postdoc Kevin McHugh and former postdoc Thanh D. Nguyen, now an assistant professor of mechanical engineering at the University of Connecticut.
The molecular weight of the PLGA polymer and the structure of the polymer molecules’ “backbone” determine how fast the particles will degrade after injection. The degradation rate determines when the drug will be released. By injecting many particles that degrade at different rates, the researchers can generate a strong burst of drug or vaccine at predetermined time points. “In the developing world, that might be the difference between not getting vaccinated and receiving all of your vaccines in one shot,” McHugh says.
In mice, the researchers showed that particles release in sharp bursts, without prior leakage, at 9, 20, and 41 days after injection. They then tested particles filled with ovalbumin, a protein found in egg whites that is commonly used to experimentally stimulate an immune response. Using a combination of particles that released ovalbumin at 9 and 41 days after injection, they found that a single injection of these particles was able to induce a strong immune response that was comparable to that provoked by two conventional injections with double the dose.
The researchers have also designed particles that can degrade and release hundreds of days after injection. One challenge to developing long-term vaccines based on such particles, the researchers say, is making sure that the encapsulated drug or vaccine remains stable at body temperature for a long period before being released. They are now testing these delivery particles with a variety of drugs, including existing vaccines, such as inactivated polio vaccine, and new vaccines still in development. They are also working on 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 says. These particles could also be useful for delivering drugs that have to be given on a regular basis, such as allergy shots, to minimize the number of injections.
Other authors on the paper are Allison Linehan, David Yang, Adam Behrens, Sviatlana Rose, Zachary Tochka, Stephanie Tzeng, James Norman, Aaron Anselmo, Xian Xu, Stephanie Tomasic, Matthew Taylor, Jennifer Lu, and Rohiverth Guarecuco.
Source: MIT News