Rethinking Medication Administration: A Pause

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image: (left) Schematic illustration showing the developed micro-needles, which absorb the interstitial fluid under the skin and release the preloaded drug. (Right) Side view image of a micro-needle loaded with rhodamine B (pink dye), which diffuses after piercing a sample of pig skin; yellow dotted lines indicate where the needles pierced the skin.
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Credit: Kazuaki Matsumura of JAIST.

Ishikawa, Japan – The painful sensation of receiving an injection through a hypodermic needle or with the unpleasant sensation of swallowing a large tablet is a generally familiar sensation. But what if a revolutionary and gentler way of administering drugs was in the works? For more than two decades, researchers have studied various types of microneedles as a minimally invasive method for transdermal drug delivery. Arrays of microneedles can be designed to be loaded with a drug or chemical, which they then release over time into the bloodstream after piercing slightly beyond the layers of the skin.

Microneedles offer several advantages over other types of drug delivery. First, they are painless and cause virtually no damage to the skin or bleeding. Second, they can be self-administered. Third, unlike traditional needles, disposing of micro needles is much easier because they do not leave hazardous waste behind. Unfortunately, there are still a few challenges ahead before microneedles become the next big innovation in healthcare. One is their cost of manufacture, which usually involves expensive molds, materials, and machinery. Another problem is the aggregation and degradation of proteins when the microneedles are preloaded with a protein drug, as these molecules are quite sensitive to external conditions such as temperature, acidity and salt concentration.

In a recent study published in Biomacromolecules, two research teams from Japan and Thailand have collaborated to remedy the main limitations of existing microneedles. On the one hand, Professor Kazuaki Matsumura from the Japan Advanced Institute of Science and Technology (JAIST) and Ph.D. student Harit Pitakjakpipop from JAIST-SIIT developed and applied a functional polymer that effectively suppresses protein aggregation. On the other side, Dr Paisan Khanchaitit and his team from the National Agency for Scientific and Technological Development (NANOTEC), Thailand, have developed a method of manufacturing micro-needles suitable for an industrial scale based on the photolithography. By combining these two efforts, the teams succeeded in producing microneedle patches with several attractive properties and potential scalability to clinical environments.

The microneedles themselves are made from a non-degradable biocompatible hydrogel which also contains zwitterionic poly-sulfobetaine (poly-SPB). As indicated in previous studies by the same authors, this polymer suppresses protein aggregation. Thus, the researchers incorporated it during the manufacturing process and showed that the proteins preloaded in the microneedles were stable even when subjected to various external stresses.

In addition, scientists have developed a simple and cost-effective way to make arrays of microneedles from the materials mentioned above. They resorted to photolithography, a process in which a photomask is used to selectively block UV light from reaching a target surface in order to control chemical reactions locally, as Dr Khanchait explains: “UV light passing through the photomask generates free radicals in the polymer resin during the manufacturing process, resulting in photopolymerization and subsequent formation of 3D microneedle structure patterns on a transparent and flexible substrate.This manufacturing procedure requires only inexpensive equipment and takes about five minutes, while producing four-pointed star-shaped micro-needles with remarkable mechanical strength.

To test the performance of these needle chips for drug delivery, the researchers loaded them with 50 microliters of drug solutions containing rhodamine B as a dye, as well as lysozyme and insulin as examples of proteins (see Figure 1). Through various experiments on pigskin, the teams verified that their microneedle patches offered both high drug load capacity and a high drug release rate. Additionally, they confirmed that micro-needles can both charge and preserve various drugs and water-soluble proteins, eliminating the need for refrigeration.

Overall, the proposed needle arrays appear to be a remarkably promising platform for the delivery of therapeutic drugs and vaccines, as Professor Matsumura concludes: “The superior characteristics of our micro-needles can alter the way drugs are delivered and could enable the development and delivery of advanced protein-based drugs for the treatment of various disorders.“Who knows what other revolutionary innovations in medicine await us in the future?

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Reference

Original article title: Easy photolithographic fabrication of a zwitterionic polymer microneedle with inhibition of protein aggregation for transdermal drug delivery
Newspaper: Biomacromolecules
DO I: 10.1021 / acs.biomac.1c01325

About Japan Advanced Institute of Science and Technology, Japan
Founded in 1990 in Ishikawa Prefecture, the Japan Advanced Institute of Science and Technology (JAIST) was the first independent national graduate school in Japan. Today, after 30 years of steady progress, JAIST has grown into one of the top universities in Japan. JAIST has several satellite campuses and strives to develop capable leaders with a cutting-edge education system where diversity is key; around 40% of its alumni are international students. The university has a unique style of higher education based on a carefully designed curriculum to ensure that its students have a solid foundation on which to conduct cutting-edge research. JAIST also works in close collaboration with local and foreign communities by promoting collaborative industry-university research.

About Professor Kazuaki Matsumura from the Japan Advanced Institute of Science and Technology, Japan
Kazuaki Matsumura is a professor at the Japan Advanced Institute of Science and Technology (JAIST). He got a doctorate. from Kyoto University in 2004. From 2006 to 2011, he worked as an assistant professor at the Institute for Frontier Medical Sciences at Kyoto University. In 2011, he became Associate Professor at the School of Materials Science of JAIST and became Full Professor in 2020. He is now a member of the Board of Trustees of the Japanese Society for Biomaterials. He has published over 120 papers in the fields of polymer science, biomaterials, and regenerative medicine, among others.

Funding Information
This work was funded in part by the Grant-in-Aid Research Grant, KAKENHI (20K20197), for Scientific Research of the Japan Society for the Promotion of Science and the National Center for Nanotechnology, National Agency for Scientific Development and technology, Thailand (P1951763).


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