Recently, a single-use self-service microneedle technology developed by UConn faculty to provide immunosuppression against infectious diseases has been validated by preclinical research trials.
Recently published in Nature Biomedical Engineering, preclinical development and testing of the microneedle fragments was reported by UConn researchers in the laboratory of Thanh Nguyen, an assistant professor in the Department of Mechanical Engineering and Biomedical Engineering.
The concept of a single injection vaccine, recognized as the best vaccination method by the World Health Organization (WHO), has been investigated for many years. Previous attempts to create a single injection vaccine include a technology called SEAL (StampEd Polymer Layer Assembly), developed in 2017 by Nguyen, to create single-injection vaccine microparticles that can produce vaccines after several defined periods , simulating multiple bolus injections.
However, these microparticles require a large needle for the injection. In addition, there are also a limited number of particles that can be loaded into the needle, meaning that only a limited vaccine dose can be delivered. Ultimately, the microparticles still require traditional injections, which are painful and produce unfavorable biohazard waste from discarded sharps. A microneedle patch held between the glowing fingers of the UConn researcher. Microneedle cloth. (Courtesy of Thanh Nguyen)
“It has long been recognized that many injections need to be eliminated in the conventional vaccination process,” said Thanh. “Although frequent vaccinations and shots of vaccines are important to maintain immune protection, these injections are associated with pain, high costs, and complex injection schedules, causing very low patient compliance. The issue is becoming more is a problem for patients in developing countries because of their limited access to healthcare providers, in such places, parents struggle to remember the schedule and cannot afford to travel long distances with their children to medical centers to receive multiple booster doses of vaccines. “
As detailed in Nature Biomedical Engineering, to overcome these problems, the Nguyen lab at UConn developed a microneedle patch of skin, which only requires one administration to perform exactly the same programmable delay in vaccine release, as that obtained from the SEAL microparticles .
The microneedle patch avoids any painful injections, offering significant patient improvement. Extensive research has shown that microneedle skin patches are virtually painless, and may even be self-administered by patients at home. The patch is small, portable, and similar to a nicotine patch, which could easily be distributed to everyone around the world for self-administration in the event of a pandemic such as a COVID-19 emergency to create immunity when rapidly the global scale.
The microneedles have a core shell microstructure, where the microneedle shells are made with FDA-approved biodegradable medical polymer for implants, and offer a unique drug-releasing kinetics – which allows release of preprogrammed vaccine batches over a period of a few days to more than a month from a single administration. The microneedles can be easily inserted and fully embedded inside the dermal layer, thanks to the miniscule tips and smooth geometry of the needles.
To create this vaccine microneedle patch, Khanh Tran, a PhD student in the Nguyen lab and lead author of the published work, adapted SEAL technology to assemble various microneedle components, including a cap, shell, and vaccine core. These components are manufactured in an additive manner, similar to 3D printing, to create arrays of core shell microneedles over a large area.
The Nguyen team devised several new approaches to overcome many of the issues of existing SEAL technology. The key novelty of their new manufacturing process is micro-vaccines to shape the microneedle core, while simultaneously inserting all molded vaccine cores in microneedle shell arrays, offering a fabrication method similar to the manufacturing process. of computer chips.
“This is a tremendous advantage, compared to the previously reported SEAL and other traditional methods of mocking vaccine carriers, where the vaccine is often slowly filled individually into each polymeric shell / carrier , “said Tran.
In the preclinical trials, the researchers inserted microneedles loaded with a clinically available vaccine (Prevnar-13) into the skin of rats in a minimally invasive manner. The patch application did not cause any skin irritation during long-term implantation, and triggered a high immune defense response against a fatal dose of infectious pneumococcal bacteria. The results of the one-time administration were similar to those of multiple injections of the same vaccine over a period of approximately two months.
“We are very excited about this achievement, because for the first time, useless skin extract and injection can be pre-programmed to release vaccines at different times to provide long-term and effective immune protection,” Nguyen said. “The microneedle patch could facilitate the global effort for a complete vaccination process to eradicate dangerous infectious diseases and enable rapid distribution of vaccines. This could create global community-wide immune protection in the event of a pandemic such as the COVID- 19, ”said Nguyen.
In this regard, Nguyen and his colleague, Associate Professor Steve Szczepanek in the Department of Pathobiology and Veterinary Science at the College of Agriculture, Health and Natural Resources, have also received a $ 432,990 contract from the US Department of Health and Human Services (HHS) BARDA to develop this technology.
Looking to the future, more research is needed to bring the microneedle cloth to clinical use. Although the researchers have shown the ability to use the patch for the pneumococcal vaccines, different strategies for stabilization would be required for different vaccines so that they can be active over a long period of implantation inside the skin.
The researchers are also working on optimizing and automating the fabrication process, which can reduce the cost of the microneedle skin patch for clinical use. Future work on larger animal models that closely mimic human immune systems is also needed to verify the safety and efficacy of microneedle platforms.
Reported articles include Szczepanek’s participation and Ph.D. student Tyler Gavitt from UConn’s Department of Pathobiology and Veterinary Science, and researchers from the Center for Advanced Science Research at the Graduate Center, City University of New York, and the Department of Chemistry at Hunter College, City University of New York.