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Hebrew University and Yissum Developing Novel Technology Platform for 3D Printing Personalized Medicine

Yissum, which is the Hebrew University of Jerusalem‘s technology transfer company and handles the patenting and commercialization of any inventions produced there, has had a hand in many unique 3D printing innovations, such as Nano Dimension’s conductive nano-inks and a process to generate hybrid machine elements. Last year, the company, which was founded in 1964 and has licensed over 900 technologies and registered over 10,000 patents covering 2,800 inventions, introduced a novel technology platform for 3D printing personalized food, and has now moved on to 3D printing personalized medicine.

The company, which is only the third of its kind, builds a bridge between academic research and its worldwide community of entrepreneurs, investors, and industry. It’s responsible for spinning more than 135 total companies. Yissum recently announced a novel technology platform for fabricating 3D printed drug capsules, and presented it today at the university’s 2nd annual 3D Printing and Beyond conference, which is sponsored by Yissum, the university, and the Jerusalem Development Authority.

Professor Shlomo Magdassi, head of the university’s 3D and Functional Printing Center and a member of the Center for Nanoscience and Nanotechnology and Institute of Chemistry, worked with Dr. Ofra Benny, a researcher at the university’s Institute for Drug Research, to develop the innovative drug 3D printing technology platform.

“Professor Magdassi and Dr. Benny’s research is an excellent example of the  kind of interdisciplinary transformational inventions that originate  from the Hebrew University,” said Dr. Yaron Daniely, CEO and President of Yissum. “This technology is bringing us closer to a future in which the medical field can offer personalized, patient-centered care.”

The technology is based on custom 3D printed hydrogels with delayed release characteristics, and allows for a complex design of drug delivery systems that is not currently available in the more traditional pharmaceutical manufacturing techniques.

Dr. Magdassi already has plenty of experience with 3D printed hydrogels and other unique 3D printable materials. 3D hydrogels are hydrophilic polymeric networks that are cross-linked by either chemical covalent bonds, physical interactions, or a combination. Because of these crosslinks between polymer chains and their hydrophilic nature, hydrogels can actually swell up to a hundred times, or even a thousand, of their dried mass without needing to be dissolved in water, and they are an ideal material for biomedical applications.

Yissum’s company mission is to take transformational technologies and innovations and convert them into commercial solutions that address the most urgent challenges in our world, in order to benefit society. I’d say this new 3D printing platform fits the bill – the approach makes it possible to 3D print customized medications out of hydrogel objects that can change shape, expand, and even activate on a delayed schedule.

The novel new 3D printing platform can not only achieve complex release profiles and structures of drugs, but it can also personalize prescription medicines, so doctors can more accurately tailor the dosage levels and exposure of medications for different patients. Thanks to 3D printing, medication may not have to be one-size-fits-all.

Professor Magdassi and Dr. Benny presented their work at the 3D Printing and Beyond conference today, which Professor Magdassi helps organize with Dr. Michael Layani. The conference brings together a range of researchers and industry leaders from around the world to discuss and learn more about the latest advances in defense-related technologies, electronics, and pharmaceuticals, in addition to 3D printed innovations like automotive parts and food.

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3D Printed Paracetamol Tablets Have Big Implications for Personalized Medicine

Drugs affect everyone differently. That’s why it’s so hard to find the right medication and right dosage to treat people with depression, for example, or why certain people don’t seem to get much relief from painkillers. That’s why the prospect of 3D printed medication is so exciting. Companies like FabRx are working to create medicines with personalized doses through 3D printing. Not only does 3D printing allow for different medications to be combined in one dose, but, as a new study shows, dosages can also be customized to suit people with different metabolic rates. The study, entitled “Extrusion 3D Printing of Paracetamol Tablets from a Single Formulation with Tunable Release Profiles Through Control of Tablet Geometry,” was written by a group of researchers from the University of Nottingham and GlaxoSmithKline.

“Personalised medicine is defined as a customization of health care to individual patients through linking diagnostics and treatments with genetic testing and emerging technologies such as proteomics and metabolomics analysis,” the researchers state. “The main advantages of this approach are to increase the effectiveness of the prescribed treatment regimen and to minimise their adverse effects such as those linked to overdosing of drugs with a narrow therapeutic index such as digoxin and anti-clotting agents.”

Paracetamol, or acetaminophen, is one of the most commonly used over-the-counter painkillers, so the researchers selected it as the subject for their proof of concept study. Work has been done before using FDM 3D printing to formulate paracetamol tablets, they note, but the high extrusion temperature limits the potential active ingredients to only heat-stable ones. Other methods like SLA and ink-jet printing use excipients that are not generally recognized as safe, however, so FDM was chosen for the study.

A regenHU 3D bioprinter was used to print paracetamol into three different tablet geometries – solid, ring and mesh. The outer dimensions of the tablets were kept in the same oval shape, but the inner geometries were varied, as were the number of layers. The weights of the tablets were also kept consistent by varying their heights. The tablet surface area influenced the speed of the drug release – for example, with the mesh tablets, 70% of the drug was released within the first 15 minutes, while 25% was released from the ring tablets and 12% from the solid tablets in the same period of time.

Notably, each of the tablets contained the same dosage of paracetamol, but the different release rates meant that they would affect people in different ways. These release rates could, therefore, be tailored to specific patients’ metabolisms for the most effective treatment.

“The demonstrated ability to use a single unmodified formulation to achieve defined release profiles presents opportunities to optimise or personalise medicines during formulation development and in clinical use,” the researchers explain. “For example, relatively straightforward personalization of medicines would be possible for individuals with different metabolism rates due to their genetic makeup for certain drugs and hence could address issues where people who metabolise drugs slowly may accumulate a toxic level of a drug in the body or in others who process a drug quickly and never have high enough drug concentrations to be effective.”

Any drug is dangerous when taken in too-high doses, but some people tend to go overboard with painkillers such as paracetamol, because, as the researchers point out, they metabolize the drugs too quickly for them to be effective and thus think that more is better. More is toxic, in fact, but programming drugs so that their release rates are tailored to each individual’s metabolism means that the same dosage can be taken by different people and still have the proper effect on each one.

If this study could be applied to painkillers only, it would still be big news, but its potential goes beyond just paracetamol. Adverse effects could be minimized from drugs such as anticoagulants and antidepressants, even as they are tailored to be more effective to each individual patient. The prospect of personalized medicine through 3D printing has a lot of promise; one day we may look back on our current “one dosage fits all” standard as primitive medicine.

Authors of the paper include Shaban A. Khaled, Morgan R. Alexander, Derek J. Irvine, Ricky D. Wildman, Martin J. Wallace, Sonja Sharpe, Jae Yoo and Clive J. Roberts.

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