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3D printed pill using a new technique CREDIT University of Nottingham, Centre for Additive Manufacturing

A new technique for 3D printing medication has enabled printing multiple drugs in a single tablet, paving the way for personalised pills that can deliver timed doses.

Researchers from the University of Nottingham’s Centre for Additive Manufacturing have led research alongside the School of Pharmacy that has fabricated personalised medicine using Multi-Material InkJet 3D Printing (MM-IJ3DP).

The team has developed a cutting-edge method for fabricating customized pharmaceutical tablets with tailored drug release profiles, ensuring patients’ more precise and effective treatment options.

Using Multi-Material InkJet 3D Printing (MM-IJ3DP), tablets can be printed that release drugs at a controlled rate, determined by the tablet’s design.  This is made possible by a novel ink formulation based on molecules sensitive to ultraviolet light. When printed, these molecules form a water-soluble structure. 

The drug release rate is controlled by the tablet’s unique interior structure, allowing for timing the dosage release. This method can print multiple drugs in a single tablet, simplifying complex medication regimens into a single dose.

Dr Yinfeng He, Assistant Professor in the Faculty of Engineering’s Centre for Additive Manufacturing led the research, he said: “This is an exciting step forwards in the development of personalised medication. This breakthrough highlights the potential of 3D printing in revolutionizing drug delivery and opens up new avenues for developing next-generation personalized medicines.” 

“While promising, the technology faces challenges, including the need for more formulations that support a wider range of materials. The ongoing research aims to refine these aspects, enhancing the feasibility of MM-IJ3DP for widespread application.” Professor Ricky Wildman added.

This technology will be particularly beneficial in creating medication that needs to release drugs at specific times. It is ideal for treating diseases where timing and dosage accuracy are crucial. The ability to print 56 pills in a single batch demonstrates the scalability of this technology, providing a strong potential for the production of personalised medicines.

Professor Felicity Rose at the University of Nottingham’s School of Pharmacy was one of the co-authors on the research, says: “The future of prescribed medication lies in a personalised approach, and we know that up 50% of people in the UK alone don’t take their medicines correctly and this has an impact on poorer health outcomes with conditions not being controlled or properly treated. A single pill approach would simplify taking multiple medications at different times, and this research is an exciting step towards that.”

Photo by engin akyurt on Unsplash

 Neuropathy, the nerve damage that causes pain and numbness in the feet and hands and can eventually lead to falls, infection and even amputation, is very common and underdiagnosed.

“More than one-third of people with neuropathy experience sharp, prickling or shock-like pain, which increases their rates of depression and decreases the quality of life,” said study author Melissa A. Elafros, MD, PhD, of the University of Michigan in Ann Arbor and a member of the American Academy of Neurology. “People with neuropathy also have an increased risk of earlier death, even when you take into account other conditions they have, so identifying and treating people with or at risk for neuropathy is essential.”

The study involved 169 people from an outpatient internal medicine clinic serving mainly Medicaid patients in Flint, Michigan. The participants had an average age of 58 years, and 69% were Black people. One-half of the people had diabetes, which can cause neuropathy. A total of 67% had metabolic syndrome, which is defined as having excess belly fat plus two or more of the following risk factors: high blood pressure, higher than normal triglycerides (a type of fat found in the blood), high blood sugar and low high-density lipoprotein (HDL) cholesterol, or “good” cholesterol. These risk factors are also associated with neuropathy.

All participants were tested for distal symmetric polyneuropathy. Information about other health conditions was also collected.

A total of 73% of the people had neuropathy. Of those, 75% had not been previously diagnosed with the condition. Nearly 60% of those with neuropathy were experiencing pain.

Of those with neuropathy, 74% had metabolic syndrome, compared to 54% of those who did not have neuropathy.

After adjusting for other factors that could affect the risk of neuropathy, researchers found that people with metabolic syndrome were more than four times more likely to have neuropathy than people who did not have the syndrome.

Researchers were also looking for any relationship between race and income and neuropathy, as few studies have been done on those topics. There was no relationship between low income and neuropathy. For race, Black people had a decreased risk of neuropathy. Black people made up 60% of those with neuropathy and 91% of those without neuropathy.

“The amount of people with neuropathy in this study, particularly undiagnosed neuropathy, was extraordinarily high with almost three-fourths of the study population,” Elafros said. “This highlights the urgent need for interventions that improve diagnosis and management of this condition, as well as the need for managing risk factors that can lead to this condition.”
A limitation of the study is that it is a snapshot in time; it did not follow people to see who developed neuropathy over time. It also did not look at why people could not manage risk factors that can lead to neuropathy.

The health benefits of exercise are well known but new research shows that the body’s response to exercise is more complex and far-reaching than previously thought. In a study on rats, a team of scientists from across the United States has found that physical activity causes many cellular and molecular changes in all 19 of the organs they studied in the animals.

Exercise lowers the risk of many diseases, but scientists still don’t fully understand how exercise changes the body on a molecular level. Most studies have focused on a single organ, sex, or time point, and only include one or two data types. 

To take a more comprehensive look at the biology of exercise, scientists with the Molecular Transducers of Physical Activity Consortium (MoTrPAC) used an array of techniques in the lab to analyze molecular changes in rats as they were put through the paces of weeks of intense exercise. Their findings appear in Nature.

The team studied a range of tissues from the animals, such as the heart, brain, and lungs. They found that each of the organs they looked at changed with exercise, helping the body to regulate the immune system, respond to stress, and control pathways connected to inflammatory liver disease, heart disease, and tissue injury. 

The data provide potential clues into many different human health conditions; for example, the researchers found a possible explanation for why the liver becomes less fatty during exercise, which could help in the development of new treatments for non-alcoholic fatty liver disease. 

The team hopes that their findings could one day be used to tailor exercise to an individual’s health status or to develop treatments that mimic the effects of physical activity for people who are unable to exercise. They have already started studies on people to track the molecular effects of exercise.

Launched in 2016, MoTrPAC draws together scientists from the Broad Institute of MIT and Harvard, Stanford University, the National Institutes of Health, and other institutions to shed light on the biological processes that underlie the health benefits of exercise. The Broad project was originally conceived of by Steve Carr, senior director of Broad’s Proteomics Platform; Clary Clish, senior director of Broad’s Metabolomics Platform; Robert Gerszten, a senior associate member at the Broad and chief of cardiovascular medicine at Beth Israel Deaconess Medical Center; and Christopher Newgard, a professor of nutrition at Duke University.

Co-first authors on the study include Pierre Jean-Beltran, a postdoctoral researcher in Carr’s group at Broad when the study began, as well as David Amar and Nicole Gay of Stanford. Courtney Dennis and Julian Avila, both researchers in Clish’s group, were also co-authors on the manuscript.

“It took a village of scientists with distinct scientific backgrounds to generate and integrate the massive amount of high quality data produced,” said Carr, a co-senior author of the study. “This is the first whole-organism map looking at the effects of training in multiple different organs. The resource produced will be enormously valuable, and has already produced many potentially novel biological insights for further exploration.”

The team has made all of the animal data available in an online public repository. Other scientists can use this site to download, for example, information about the proteins changing in abundance in the lungs of female rats after eight weeks of regular exercise on a treadmill, or the RNA response to exercise in all organs of male and female rats over time.

Whole-body analysis

Conducting such a large and detailed study required a lot of planning. “The amount of coordination that all of the labs involved in this study had to do was phenomenal,” said Clish.

In partnership with Sue Bodine at the Carver College of Medicine at the University of Iowa, whose group collected tissue samples from animals after up to eight weeks of training, other members of the MoTrPAC team divided the samples up so that each lab — Carr’s team analyzing proteins, Clish’s studying metabolites, and others — would examine virtually identical samples.

“A lot of large-scale studies only focus on one or two data types,” said Natalie Clark, a computational scientist in Carr’s group. “But here we have a breadth of many different experiments on the same tissues, and that’s given us a global overview of how all of these different molecular layers contribute to exercise response.”

In all, the teams performed nearly 10,000 assays to make about 15 million measurements on blood and 18 solid tissues. They found that exercise impacted thousands of molecules, with the most extreme changes in the adrenal gland, which produces hormones that regulate many important processes such as immunity, metabolism, and blood pressure. The researchers uncovered sex differences in several organs, particularly related to the immune response over time. Most immune-signaling molecules unique to females showed changes in levels between one and two weeks of training, whereas those in males showed differences between four and eight weeks.

Some responses were consistent across sexes and organs. For example, the researchers found that heat-shock proteins, which are produced by cells in response to stress, were regulated in the same ways across different tissues. But other insights were tissue-specific. To their surprise, Carr’s team found an increase in acetylation of mitochondrial proteins involved in energy production, and in a phosphorylation signal that regulates energy storage, both in the liver that changed during exercise. These changes could help the liver become less fatty and less prone to disease with exercise, and could give researchers a target for future treatments of non-alcoholic fatty liver disease.

“Even though the liver is not directly involved in exercise, it still undergoes changes that could improve health. No one speculated that we’d see these acetylation and phosphorylation changes in the liver after exercise training,” said Jean-Beltran. “This highlights why we deploy all of these different molecular modalities — exercise is a very complex process, and this is just the tip of the iceberg.”

“Two or three generations of research associates matured on this consortium project and learned what it means to carefully design a study and process samples,” added Hasmik Keshishian, a senior group leader in Carr’s group and co-author of the study. “Now we are seeing the results of our work: biologically insightful findings that are yielding from the high quality data we and others have generated.That’s really fulfilling.”

Other MoTrPAC papers published today include deeper dives into the response of fat and mitochondria in different tissues to exercise. Additional MoTrPAC studies are underway to study the effects of exercise on young adult and older rats, and the short-term effects of 30-minute bouts of physical activity. The consortium has also begun human studies, and are recruiting about 1,500 individuals of diverse ages, sexes, ancestries, and activity levels for a clinical trial to study the effects of both endurance and resistance exercise in children and adults.