New Test Syringe Prevents Clogging, Increasing Microparticle Delivery Sixfold

07/01/2020
Test Syringe Prevents Clogging

Engineers at the Massachusetts Institute of Technology (MIT) have created a computer model of a new syringe that could prevent clogging and increase microparticle output during injections. Microparticles are only about the size of one grain of sand. However, it can be difficult to inject them if they become clogged in a syringe. This prevents delivery of medications, drugs, and even vaccines as they are being administered. Researchers at MIT have developed a new computer model that analyzes several factors, including particle sizes and shapes, to determine the most optimal syringe design.

Other factors that may influence clogging include the viscosity of the solution needed to encompass the particles and the shape and size of the syringe and needle used to deliver the application. The most important factors that the MIT researchers need to take into account are particle size, solution viscosity, particle concentration in the solution, and the size of the needle. The new model allows an increase of sixfold in the percentage of microparticles that can successfully be injected into the user. This gives researchers hope that they can test and develop microparticles that can possibly be used in cancer immunotherapy drugs, among others.

According to Ana Jakenec, MIT Koch Institute for Integrative Cancer Research scientist, this new model is the framework that can help MIT with technology that they’ve developed in the lab and are trying to get in the clinic. The team designed an optimal shape for the syringe that looks like a nozzle with a wide taper near the tip. During tests, the research team discovered that this new syringe increased particle delivery from 15% to almost 90%. The team hopes that his new research can be used in the treatment of cancer drugs, vaccines, and other drugs, including small-molecule biologics and more.

The funding for the project was provided by the Bill and Melinda Gates Foundation, a National Institute of Health Ruth L. Kirschestein National Research Service Award, and the Koch Institute Support Grant from the National Cancer Institute. According to Morteza Sarmadi, graduate student and lead author of a research paper on the new project that appears in Science Advances, the team is trying to maximize the force that pushes down on the particles and pushes them toward the needle. The results are promising because it shows that there is lots of room for improvement within the injectability of systems involving microparticles, Sarmadi continued.

Microparticle Clogging Leads To Drug Failures

Microparticles are promising because they offer a way to deliver several doses of a vaccine or drug in one application. They can also be designed to release the drug or vaccine at a certain time. However, even though the particles are so small, they can still become lodged in a typical syringe and become clogged, which reduces the amount of intended drug or vaccine to the recipient. MIT’s new syringe model provides a work around for this problem to ensure that every application is administered as intended with appropriate doses.

Senior authors of the study include Ana Jakenec, research scientists at the Koch Institute for Integrative Cancer Research, and Robert Langer, MIT Professor at the David Koch Institute. The computational model works by preventing clogging to improve particle injectability. Microparticles vary in size from 1 to 1,000 microns, or millionths of a meter. Many scientists are performing research on how to use microparticles made of polymers and other materials to administer drugs. The FDA has only approved about a dozen of these drug formulas. The rest have failed because there are so many problems surrounding the administration of their injections.

Jaklenec stated that clogging somewhere in the system is a major issue among these formulas, which means that the full dose cannot be delivered. Drugs that have a problem with injectability do not make it past the development phase. These drugs are usually injected under the skin or intravenously. It’s important to make sure that these drugs successfully reach their destination. Otherwise, they will not be considered in the drug development process. However, this step is often the last to be considered and can cause an otherwise promising treatment to fail.

Injectability Matters

According to Sarmadi, injectability is a big factor when it comes to determining how successful a drug will be. However, many developers do not pay enough attention to improving the administration techniques of a drug. He stated that he hopes the team at MIT can improve this aspect for both novel and advanced drug formulas with controlled-release technology. Jaklenec and Langer have been working on creating hollow microparticles that can be filled with several doses of a vaccine or drug. This would allow the particles to release their contents at different times, potentially eliminating the need for more than one injection.

Researchers are improving the injectability of microparticles by analyzing the effects of different shapes and sizes. They also experiment with the shape and size of the syringe and needle used to inject the drugs, and the viscosity of the liquid that they are suspended in. The researchers are also testing spheres, cubes, and cylindrical particles of different sizes and measuring how well each unit’s injectability is.

The team then uses this data and puts it into a computer model known as a neural network, which predicts how each of these parameters will affect the injectability of the solution. The team determined that the size of the needle, the viscosity of the solution, the particle concentration within the solution, and the particle size were the most important factors used to increase a solution’s injectability.

Other researchers who are working on microparticles for drug delivery can use these parameters in their models to predict how injectable their solutions will be. This would help save them time and prevent the need to build different versions of the particles while testing them individually. Sarmadi stated that instead of going through the process with different experiences and having no idea how successful each one will be, researchers can use the neural network to guide them through early on so that they have a better understanding of the system.

The team at MIT also used their new model to determine how changing the shape of the syringe may affect injectability. Using this technique, they determined an optimal shape for the syringe that best supports injectability, which looks like a nozzle with a wide diameter that slims down near the tip. The researchers used this syringe design to test the injectability of microparticles described in a 2017 study published in Science, which found that particle injectability increased from 15 percent to nearly 90 percent.

Past Research With “Sealed Cups” Coupled With New Technology Could Turn Several Shots Into One

This new syringe technology has the potential to turn several shots or vaccines that are usually delivered over an extended amount of time into one injection. MIT has worked with similar particles in the past that look like small coffee cups that are filled with a vaccine or drug and closed with a lid. They are made with an FDA-approved, biocompatible polymer and they can be designed to release at certain times to spill out of its container.

According to Langer, the project allowed researchers to create a library of tiny, enclosed particles that are each designed to release at predictable, precise times. This means that doctors could turn several boosts into one injection to cut down on application uses, which could have a significant impact on people all over the world. This technology is especially useful for developing parts of the world where patient compliance is not well. It would also be beneficial for babies to receive all of their intended vaccines in developing nations who might not see a doctor regularly.

Langer has experience working with polymer particles embedded with drugs that are intended to be released over time. However, the researchers wanted to find a way to deliver short bursts of drugs at specific times to mimic the way a vaccine would work. To do this, they developed a sealable polymer cup made from a biocompatible polymer called PLGA, which has been approved for different uses, such as prosthetic devices, sutures, and implants. Then the team used conventional 3D printing techniques to determine the best size and material for the cups.

In the past, MIT researchers tested the sealed cups and determined that the particles were released in sharp bursts without leaking beforehand at 9, 20, and 41 days after being injected. The particles were tested with a substance called ovalbumin, which is an egg white protein that stimulates an immune response. The researchers found that a single injection of the particles produced a strong enough immune response that was comparable to two injections with double doses. MIT has also designed particles that can be released hundreds of days after being injected.

However, the challenge of developing long-term vaccines based on these particles is tough as they need to make sure the drug remains stable at body temperature for long periods before being released. They are working on stabilizing the vaccines and testing new deliveries for particles with a variety of drugs. The new syringe technology, coupled with the past research MIT has conducted on particles, could change the way people are administered vaccines in the future.