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World News – AU – Evidence of Viability of Injection-Free Microneedles for One-Time Vaccine Administration

. . A self-administered, disposable microneedle technology for immunization against infectious diseases developed by the UConn faculty has recently been validated through preclinical research studies.

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23. November 2020

by Courtney Chandler, University of Connecticut

A self-administered, disposable microneedle technology for immunization against infectious diseases developed by the UConn faculty has recently been validated through preclinical research studies.

Recently published in Nature Biomedical Engineering, UConn researchers in the laboratory of Thanh Nguyen, assistant professor in the mechanical engineering and biomedical engineering departments, reported on the development and preclinical testing of the microneedle patches.

The concept of a single injection vaccine, recognized by the World Health Organization (WHO) as the preferred vaccination approach, has been explored for many years. Previous efforts to develop such a vaccine with one injection included a technology called SEAL (StampEd Assembly of Polymer Layer), developed by Nguyen in 2017, to make microparticles for vaccines with one injection, which vaccines can deliver after several defined periods of time and simulate multiple bolus injections.

However, these microparticles require a large needle for injection. In addition, there are also a limited number of particles that can be loaded into the needle, which means that only a limited dose of the vaccine can be delivered. Ultimately, the microparticles still require traditional injections, which are painful and produce unfavorable biohazardous waste from discarded sharp syringes. A tiny microneedle dot is held between the gloved fingers of a UConn researcher. A microneedle plaster. (Courtesy Thanh Nguyen)

« It has long been known that it is necessary to eliminate many injections in the conventional vaccination process, » says Thanh. « While boosters and repeated vaccinations are important to maintain immune protection, these injections are painful, costly, and complicated injection schedules, resulting in very poor patient compliance. The problem is becoming more problematic for patients in developing countries because of their limited access to health care providers. In such places, parents have difficulty remembering the schedule and cannot afford to repeatedly drive long distances with their children to medical centers for multiple booster doses of vaccines. « 

As detailed in Nature Biomedical Engineering, to overcome these problems, Nguyen’s laboratory at UConn developed a microneedle skin patch that required only a single administration to deliver the exact same programmable sustained release vaccine that the SEAL microparticles was obtained.

The microneedle plaster avoids painful injections and offers a significant improvement from the patient’s point of view. Extensive research has shown that microneedle skin patches are virtually painless and can even be administered by patients themselves at home. The patch is small, portable, and resembles a nicotine patch that, in the event of a pandemic like the COVID-19 crisis, can be easily distributed for self-administration to all people around the world to quickly create immunity to pan on the global scale.

The microneedles have a core-shell microstructure in which the microneedle shells are made from biodegradable medical polymer that is FDA approved for implants and offer unique drug release kinetics that provide a preprogrammed burst release of vaccine charges over a period allows periods from a few days to more than a month from a single administration. Thanks to the tiny tips and the smooth geometry of the needles, the microneedles can be easily inserted and completely embedded in the skin layer.

To make this vaccine microneedle patch, Khanh Tran, a Ph. D.. . The student in Nguyen’s lab and lead author of the published work adapted SEAL technology to assemble various microneedle components, including a cap, a sheath, and a vaccine core. These components are manufactured in an additive manner, similar to 3D printing, in order to create large-scale arrangements of core-shell microneedles.

The Nguyen team developed several new approaches to solve many problems in the existing SEAL technology. The main novelty of their new manufacturing process is to microform vaccines into the shape of the microneedle core and insert all the shaped vaccine cores into arrays of the microneedle shells at the same time, offering a manufacturing process similar to the process of manufacturing computer chips, as shown in this video: Video Player00: 0000: 50

« This is a huge advantage compared to SEAL and other traditional methods of making vaccine carriers, which often slowly pour the vaccine into each polymer shell / carrier, one at a time, » says Tran.

In the preclinical studies, 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 caused no skin irritation during long-term implantation and triggered a high immune protective reaction against a lethal dose of infectious pneumococcal bacteria. The single dose results were similar to those obtained with multiple injections of the same vaccine over a period of approximately two months.

« We are very pleased with this achievement, as for the first time a one-time and injection-free skin patch can be preprogrammed to release vaccines at different times and to ensure long-term and effective immune protection. « Says Nguyen. « The microneedle patch could facilitate global efforts to have a full vaccination process to eradicate dangerous infectious diseases and allow vaccines to be distributed quickly. This could create global immune protection across the community in the event of a pandemic like COVID-19, « says Nguyen.

In that regard, Nguyen and his associate, Associate Professor Steve Szczepanek in the Department of Pathobiology and Veterinary Sciences at the College of Agriculture, Health and Natural Resources, also have a contract for 432. Received 990 USD from the U.. S.. . Department of Health and Human Services (HHS) BARDA to develop this technology.

Looking to the future, further research is needed to bring the microneedle patch into clinical use. While the researchers demonstrated the ability to use the patch for the pneumococcal vaccines, different vaccines would require different stabilization strategies in order for them to function over long periods of implantation in the skin.

The researchers are also working to optimize and automate the manufacturing process, which can reduce the cost of the microneedle skin patch for clinical use. Future work on larger animal models that strongly mimic the human immune system is also needed to validate the safety and effectiveness of the microneedle platforms.

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Vaccine, Injection, Vaccination, Research, Biomedical Technology

World News – AU – Evidence of Viability of Injection-Free Microneedles for Single Vaccine Administration
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