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Researchers seek to apply nanoparticle drug delivery to coral wound healing
Coral reefs are the foundation of many aquatic ecosystems and are among the ocean’s most vulnerable inhabitants. While natural processes, like animal predation and storms, frequently damage coral, man-made causes, like ship collisions and global warming, destabilize these environments beyond their ability to recover. Researchers like Nastassja Lewinski, Ph.D., associate professor of chemical and life science engineering, are working to understand how corals heal in order to aid the restoration of these fragile ecosystems. They also seek partnerships with stakeholders that can support coral preservation by applying this research to industry practices and providing funding for continued research. “Coral ecosystems are vital to human life,” Lewinski said, “When there’s a high-intensity storm, reefs can absorb the impact and reduce the damage we see on land. They’re also important to the aquatic food web and serve as the foundation to many foods we eat.” Discovering the limits of coral healing is part of Lewinski’s work. Ideal water temperature for coral is 25 degrees Celsius, so research is conducted at the ideal temperature and elevated temperatures of 28 to 31 degrees Celsius, the projected water temperatures influenced by global warming. Successive imaging of wound closure in these conditions builds an understanding of the rate of closure during healing. “We’re looking to understand the mechanics of healing,” Lewinski said, “Some of what we’ve found suggests a process similar to human healing. We want to understand the actors in this process at a cellular level and what their role is in repairing tissue.” These observations inform the mathematical, cell-based wound healing model developed by Lewinski’s collaborators, Angela Reynolds, Ph.D. and Rebecca Segal, Ph.D., both professors in the Department of Mathematics and Applied Mathematics in VCU’s College of Humanities and Sciences. Similar to humans, corals have been documented as following the same four stages of the healing process. These stages include: 1) coagulation to close the site of injury, 2) infiltration with immune cells to ward off infection, 3) cell migration and proliferation and 4) scar remodeling. “With our observations and a mathematical model, the next step is to collect data on the cellular dynamics of the healing process,” Lewinski said, “We want to observe what kinds of cells enter the wound area and what functions they perform during healing.” Fluorescent tagging is used to mark specific cells so they may be observed entering the wound area when healing occurs. Because corals are naturally fluorescent, the selection of the fluorescent tags must take this into account. Phagocytic properties allow immune cells to engulf and absorb bacteria and other small cells, in this case the fluorescent particles being used to tag immune cells. Nutritional variables are also being considered within the experiment. Corals derive energy from consuming small organisms and their symbiotic relationship with algae colonies. Modifying nutritional balance in the lab emulates the coral’s participation in the food web, where accessibility to vital nutrients could impact healing. Developing a nanoparticle drug-delivery system designed to deliver molecules to speed wound healing is the culmination of this research. Lewinski hypothesizes the delivery system would promote an energy-burning state within the corals that could result in increased healing. This is among a few examples of harnessing nanotechnology for safeguarding coral reefs, which are discussed in a recently published comment in Nature Nanotechnology. “The research we’re doing on wound healing in corals is the start of something bigger,” Lewinski said. “Our goal is to create a center dedicated to engineering new technologies for corals. We want to find partners who can translate our research findings to practice, helping preserve coral reefs and the vital resources they provide.” Through this consortium, newly-developed science can be disseminated more effectively within each partner’s respective industry. The result: a renewed commitment to aquatic sustainability and the protection of vital coral ecosystems.
Aston University partners with paediatric pharmaceutical company to facilitate student research
• Aston University MSc Pharmaceutical Sciences, Drug Delivery and MPharm students work with industry professionals on research projects • Proveca pharmaceutical specialises in the development and licensing of medicines for children • Students will attend workshops led by Proveca and receive coaching on their research proposals. Aston University has partnered with pharmaceutical company Proveca to help support and facilitate final research projects being undertaken by its MSc Pharmaceutical Sciences, Drug Delivery and MPharm students. The partnership between the College of Health and Life Sciences at Aston University and Proveca began with a contract research project during which Professor Afzal Mohammed worked with Proveca to explore the development of drug formulation. Proveca is a pharmaceutical company specialising in the development and licensing of medicines for children. The company has now come on board to support and supervise at least five final year research projects and will help steer the students in the next steps in their lab research. The company will also support a wider number of students by running workshops, educating them on the current challenges of drug formulation development and providing coaching on how to write a research proposal. Professor Afzal Mohammed, associate head of pharmacy at Aston University, said: “This is a fantastic opportunity to enhance the student experience and build on our excellent industry focused teaching and research”. The projects are due to start in January 2023 and Proveca has agreed to sponsor the final project prize open to all of our MSc Pharmaceutical Sciences, Drug Delivery and final year MPharm students. Dr Simon Bryson, CEO and founder of Proveca Ltd, said: “We are delighted to be building on our relationship with Aston University, having collaborated over several years on a range of successful projects including PhD sponsorship and supervision, visiting lecturing and MPharm research awards. “The partnership brings together the academic excellence of Aston University with the paediatric pharmaceutical expertise of Proveca which will ultimately drive innovation in paediatric medicines to improve child health.” For more information about the School of Pharmacy at Aston University please visit our website.
Worth Longest research on more targeted aerosol drug delivery systems
Michael Hindle, Ph.D., a professor in the VCU Department of Pharmaceutics, and P. Worth Longest, a professor in the VCU Department of Mechanical and Nuclear Engineering, have invested years of time and millions of dollars to address challenges found in the field of medical aerosols. In particular: While smaller particles are more effective in delivering drugs into the lungs and airways, these tiny particles are often exhaled out immediately when taking a dose. Current aerosol delivery systems — think asthma inhalers — effectively deliver just 10 percent of an aerosolized dose. That’s fine for most asthma and COPD sufferers who use standard inhalers with existing medications, as these patients only need a small amount of the potent drugs to reach the lungs and have an effect. “But the medical world wants to use the lungs for delivery of other drugs, whether it’s locally to the airways or systemically to the body, and for that, you need more efficient devices,” Hindle says. To effectively use inhaled drugs for complex medical conditions requires more of the aerosol to reach the airways and to potentially target different regions of the airways — plus the devices to get them there. “Our work is about doing something different — changing that ballgame from having 90% of the drug wasted and 10% make it to the lungs, and flip it so that we get just 10% lost and 90% in the lungs,” Hindle says. “That’s always been our goal.” Taking aerosols from lab to lung Over more than a decade, the duo and their teams have created the three keys to making aerosol drug-delivery work: “developing the strategy, developing the device, and developing the formulation,” says Longest, the College of Engineering’s Louis S. and Ruth S. Harris Exceptional Scholar Professor. “When you see inhalation of aerosols fail, or a new pharmaceutical aerosol product fail, one of these areas has often been neglected. Between my lab and the Hindle lab, we have expertise in each of these different areas.” The fourth component — commercializing their inventions — is underway through a partner in Quench Medical in a deal signed in 2020 thanks to VCU Innovation Gateway. The Minnesota-based company, led by founder and CEO Bryce Beverlin II, Ph.D., has identified lung cancer, severe asthma, and cystic fibrosis as potential initial applications using VCU’s intellectual property, the licensing of which covers both the aerosols and the delivery devices. “It’s very difficult for an academic institution to develop a drug product,” says Hindle, the Peter R. Byron Distinguished Professor in Pharmaceutics. “So Bryce has moved forward with a team of manufacturers, clinical testing plans, and is talking to the Food and Drug Administration.” The VCU researchers had not previously pursued lung cancer as a possible application until Quench came along, Hindle says. “The idea that you could deliver a chemotherapy locally to the lungs is obviously very advantageous, because you don’t get the systemic side effects through the body like with traditional chemotherapy,” he says. “You’re just delivering drugs direct to that site of action for targeting the metastases in the lung.” In May, Quench presented data using the VCU technology to the Respiratory Drug Delivery conference in Florida showing that using a chemotherapeutic dry powder aerosol in rats was highly effective. It significantly reduced tumor burden but used half of the standard IV-delivered chemo dose. “This approach also aims to decrease the total drug delivered with reduced systemic drug levels in the circulation to decrease systemic toxicity,” the report read. It noted the efforts “solve a critical unmet medical need to develop new strategies to improve treatment outcomes in patients with lung cancer.” Heavy interest nationally Hindle and Longest have millions of dollars in funded projects underway, backed by the National Institutes of Health, U.S. Food & Drug Administration, and the Bill & Melinda Gates Foundation. Their work is building on the reputation of VCU’s Aerosol Research Group, founded in 1988 by emeritus professor Dr. Peter Byron (the name on Hindle’s professorship). The group’s work spans a wide variety of research areas in aerosol formulation and delivery. Hindle and Longest have worked together since 2006. While Hindle is focused on drug formulations, Longest is the engineering and computer modeling expert. His background is in biological fluid flow, and prior to joining VCU in 2004 had worked in the area of blood flow in vascular disease. But he wanted to differentiate his work, and found VCU’s reputation in medical aerosols was the place he could, in his words, “make an impact.” Through computer models, Longest and his team can understand how powders or liquids will turn into aerosol particles and the behaviors they will undertake when delivered into the body. “The lung is an area of the body where we have all these complex phenomena occurring with airflow and moving walls,’” he says. “It really takes high performance computers to understand it.” Drs. Longest and Hindle have developed a series of technology platforms that produce particles that are tiny when entering the lungs to minimize deposition losses in the mouth and throat — but grow in size as they travel down the warm, humid airways. One of the devices uses a mixer-heater to produce tiny particles, other technologies use a pharmaceutical powder or liquid containing a simple hygroscopic excipient such as sodium chloride; it is this excipient that attracts water from the lungs and makes the particles grow and deposit in the lungs with high efficiency. Eyes on infants Lately, the pair have been working on a method of aerosol drug delivery to newborns and prematurely born babies. “It’s a different set of challenges when you’re trying to deliver aerosols to infants who are born prematurely, and don’t have the ability to breathe on their own due to the lack of airway surfactant,” Hindle says. “And that’s something that, academically, we thought we were in a position to try and make a contribution to the field.” The group is working with funding from the NIH and the Bill and Melinda Gates Foundation to develop a method of delivering an aerosol surfactant to infants that will hopefully remove the need to intubate these fragile babies. In addition to striking licensing deals with Quench and building relationships with additional partners, Innovation Gateway has backed the pair’s work with an initial $25,000 from VCU’s Commercialization Fund as well as a just-awarded additional $35,000. “We turned that into a series of intellectual property that has resulted in three licensed patents and a whole family of IP in relation to both formulations and devices,” Hindle says. “There’s been lots of interest in delivering drugs to the lungs, it’s just been very difficult to institute any sea change, because the pharmaceutical industry is relatively risk averse.” And so their research continues, as Quench moves forward to bring their inventions to the bedside. “What I’m doing, I don’t really consider it work — it’s an opportunity to interact with great colleagues and contribute to a mission that will be very helpful to a broad range of people,” Longest says. “I also see it as a big responsibility. We want to do this in the right way. Because people’s health and lives are at stake. We want to make sure we approach this with a large sense of responsibility, and do our best.”
Aston University researchers based in the College of Health and Life Sciences have been awarded a Knowledge Transfer Partnership (KTP) project by Innovate UK, to bring its academic and scientific expertise to assist Catalent in the development of its Zydis® technology, the leading orally disintegrating tablet (ODT). The Zydis ODT fast-dissolve formulation is a unique, freeze-dried oral solid dosage form that disperses almost instantly in the mouth with no water required. It helps delivering treatments to patients and consumers who have difficulty swallowing conventional pills, or where rapid onset of action is desirable. The aim of the KTP partnership is to develop and prove an accurate predictive decision-making tool to pre-determine accurate levels of absorption enhancer for each Zydis product, potentially facilitating faster pharmaceutical development, improving efficiency, and reducing time to market. A Knowledge Transfer Partnership (KTP) is a three-way collaboration between a business, an academic partner and a KTP Associate. The UK-wide programme helps businesses to improve their competitiveness and productivity through the better use of knowledge, technology and skills. Aston University is the leading KTP provider within the Midlands. Academic lead on the project is Professor Afzal Mohammed, who is also chair in Pharmacy in the College of Health & Life Sciences (HLS) and a member of the Aston Pharmaceutics Group (APG) at Aston University. Afzal said: “This is a great opportunity for us to share and translate our academic experience in cell based models, excipient and formulation characterisation to develop an evidence based predictive tool that has the potential to expedite product development at Catalent.” Ralph Gosden, head of Zydis product development at Catalan, added: "We are excited to be working with Aston University on this project. Their expertise in drug transportation, cell biology, data analysis and model cell line design, coupled with its world-class facilities means that together, we will be able to achieve significant improvements in efficiency, and accelerate new product development.” Professor Mohammed will be supported by other colleagues from the Aston Pharmaceutics Group, including, Dr Dan Kirby, who has experience in drug delivery and improving patient acceptability of dosage forms gained through original research; Dr Affiong Iyire who has research expertise in the formulation of drugs for pre-gastric absorption and innovative cell models; and Dr Raj Badhan, who is a pharmacokinetics expert with vast knowledge of in silico methods. The outcomes of the project will be integrated into Aston University’s curriculum through teaching case studies, thereby developing well equipped graduates.
Metal-Breathing Bacteria Could Transform Electronics, Biosensors, and More
When the Shewanella oneidensis bacterium “breathes” in certain metal and sulfur compounds anaerobically, the way an aerobic organism would process oxygen, one of the materials it can produce is molybdenum disulfide, a material that could be used to enhance electronics, electrochemical energy storage, and drug-delivery devices. Shayla Sawyer, an associate professor of electrical, computer, and systems engineering at Rensselaer, has centered much of her research on the unique abilities of this bacterium. Her lab’s exploration in this area could be an important step toward developing a new generation of nutrient sensors that can be deployed on lakes and other water bodies. Compared with other anaerobic bacteria, one thing that makes Shewanella oneidensis particularly unusual and interesting is that it produces nanowires capable of transferring electrons. “That lends itself to connecting to electronic devices that have already been made,” Sawyer said. “So, it’s the interface between the living world and the manmade world that is fascinating.” Sawyer is available to talk about this unique and innovative area of research, and the potential to develop the next generation of electronics and sensors.
Gene therapy and the next frontier of medicine
Genetic testing today is mainstream, marketing to consumers who want to know where in Europe they came from or what types of hereditary diseases they could develop. For around $200 you can trace your family tree to learn your origins or identify genetic abnormalities that could signal disease. James Dahlman, assistant professor in the College of Engineering’s biomedical engineering department, specializes in genetics and believes these genotyping services can be helpful, as long as they are used responsibly. “If you’re going to start making medical predictions, you have to be careful,” said Dahlman. “Most people are not equipped to interpret statistics correctly, which can lead to negative predicting and ethical dilemmas. In a few years, genetic counselors will be in high demand so folks can make better decisions about their health.” Dahlman is fascinated by genetics, citing gene therapy as the most interesting field in the world. And it’s a field that he is revolutionizing through his research. Gene therapy is an experimental technique that uses genes to treat or prevent diseases, including hemophilia, Parkinson’s, cancer and HIV. It can help manage a number of diseases by leveraging genes instead of drugs or surgery. Although gene therapy shows promise, there are still risks involved, including unwanted immune system reactions or the risk of the wrong cells being targeted. That’s where Dahlman’s research comes in. Dahlman’s lab focuses on drug delivery vehicles, which are nanoparticles. The nanoparticle delivers gene therapies to the right place in the body to fight disease. It’s critical that the gene therapies only target the unhealthy cells to avoid damaging healthy ones. Dahlman is laser focused on ensuring the nanoparticles know what paths to take to reach the correct organ to start the healing process. “The issue with genetically-engineered drugs is that they don’t work unless they get to the right cell in the body,” said Dahlman. “You can have the world’s best genetic drug that's going to fix a tumor or eradicate plaque, but it’s not going to be effective unless it travels to the right organ. In my lab, we design different nanoparticles to deliver the genetically-engineered drugs to the correct location.” The field of genetic therapy is fascinating – and if you are a journalist looking to cover this topic or have questions for upcoming stories – let our experts help. James Dahlman is an Assistant Professor in the Georgia Tech BME Department. He is an expert in the area of biomedical engineering and uses molecular biology to rationally design the genetic drugs he delivers. This research is redefining the field of genetic therapy. Dr. Dahlman is available to speak with media – simply click on his icon to arrange an interview.
