Tuesday , January 26 2021

New technology may provide immunization against infectious diseases



The single-use, self-administration microneedle technology developed by UConn to provide immunization against infectious diseases has recently been validated in preclinical research studies.

Recently published in Biomedical engineering of natureThe development and preclinical studies of microneedle patches have been described by UConn researchers at the laboratory of Thanh Nguyen, assistant professor in the Department of Mechanical Engineering and Biomedical Engineering.

The concept of single injection vaccine, recognized by the World Health Organization (WHO) as the preferred approach to vaccination, has been studied for many years.

Earlier efforts to create such a single injection vaccine include a technology called SEAL (StampEd Assembly of Polymer Layer), developed in 2017 by Nguyen, to create single injection vaccine microparticles that can deliver vaccines after several specific periods by simulating multiple bolus injections.

However, these microparticles require a large injection needle. In addition, there are also a limited number of particles that can be inserted into the needle meaning that only a limited dose of the vaccine can be administered.

Ultimately, microparticles still require traditional injections, which are painful and generate unfavorable biohazardous waste from discarded sharp syringes. A small microneedle patch held between the fingers of the UConn researcher’s gloves. Micro-needle patch. (Courtesy of Thanh Nguyen)

It has long been recognized that there is a need to eliminate multiple injections in the conventional vaccination process. While booster doses and repeated doses of vaccines are important to maintain immune protection, these injections are associated with pain, high cost, and complicated injections. schedules, resulting in very poor patient compliance“.

Thanh Nguyen, Assistant Professor, Department of Mechanical Engineering and Biomedical Engineering, University of Connecticut

The problem is becoming more problematic for patients in developing countries due to their limited access to health professionals. In places like this, parents have a hard time remembering a schedule and cannot afford to repeatedly travel long distances with their children to medical facilities to receive multiple booster doses of vaccines.

As detailed in Biomedical engineering of natureTo overcome these problems, the Nguyen lab at UConn developed a microneedle patch that only requires one injection to perform exactly the same programmable delayed vaccine release as that obtained from SEAL microparticles.

The microneedle patch avoids painful injections, offering significant improvements from the patient’s point of view.

Extensive research has shown that microneedle patches are almost painless and can even be self-administered by patients at home.

The patch is small, portable and similar to a nicotine patch that can be easily distributed to all people around the world for self-administration in the event of a pandemic such as the COVID-19 crisis, to rapidly build global immunity.

Micro-needles have a core-shell microstructure in which the microneedle shells are made of a biodegradable medical polymer that is FDA approved for use in implants and offers unique drug release kinetics – allowing for programmed rapid release of a vaccine dose for a period ranging from a few days to over month from a single administration.

The microneedles are easy to insert and completely sink into the skin layer thanks to the tiny tips and the smooth geometry of the needles.

To create this vaccine microneedle patch, Khanh Tran, a PhD student at the Nguyen lab and lead author of the published work, adapted SEAL technology to assemble various microneedle components, including the cap, shell, and vaccine core.

These components are produced additively, similar to 3D printing, to create a matrix of core-shell microneedles over a large area.

The Nguyen team developed several new approaches to solve many of the problems with existing SEAL technology.

A key novelty in their new manufacturing process is micro-mold in the shape of a micro-needle core and the simultaneous placement of all formed vaccine cores in microneedle shell sets, offering a manufacturing method similar to the computer chip manufacturing process.

“This is a tremendous advantage over previously described SEALs and other traditional vaccine carrier production methods where the vaccine is often slowly incorporated into each polymer coating / carrier,” says Tran.

In preclinical studies, scientists introduced microneedles loaded with a clinically available vaccine (Prevnar-13) into the skin of rats in a minimally invasive manner.

Application of the patch did not cause skin irritation during long-term implantation and triggered a strong immune response against a lethal dose of infectious pneumococcal bacteria.

The results after a single dose were similar to the results obtained after 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, a disposable, non-injectable skin patch can be programmed to release vaccines at different times to provide long-lasting and effective immune protection,” says Nguyen.

“A microneedle patch could facilitate a global effort to complete the vaccination process to eradicate dangerous infectious diseases and enable the rapid distribution of vaccines. This could create a community-wide global immune defense in the event of a pandemic like COVID-19, ”says Nguyen.

As such, Nguyen and his associate Associate Professor Steve Szczepanek of the Department of Pathobiology and Veterinary Sciences at the College of Agriculture, Health and Natural Resources 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 introduce the microneedle patch into clinical use. While scientists have demonstrated the ability to use the patch for pneumococcal vaccines, different vaccines would require different stabilization strategies in order to be effective over long periods of implantation into the skin.

Scientists are also working on optimizing and automating the manufacturing process, which could lower the cost of a microneedle patch for clinical use.

Future work on larger animal models that closely mimic the human immune system is also needed to validate the safety and effectiveness of microneedle platforms.

Source:

University of Connecticut

Journal reference:

Tran, KTM, et al. (2020) Transdermal microneedles for programmable, serial release of multiple vaccine loads. Biomedical engineering of nature. doi.org/10.1038/s41551-020-00650-4.


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