Targeting the lymphatic system as a new gateway for effective drug delivery
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Targeting the lymphatic system as a new gateway for effective drug delivery
The lymphatic system is a vitally important network within the body. While its most obvious functions have been known for a long time, it plays a range of other important roles that are only just coming to light. Professor Natalie Trevaskis, a pharmaceutical scientist at Monash University in Australia, is studying one of these new discoveries: how the lymphatic system could deliver drugs more effectively than the bloodstream.
Talk like a pharmaceutical scientist
Cardiovascular system — the heart and network of blood vessels that transport substances around the body
Lipid — a fat molecule
Lymph — the clear fluid that drains from tissues through lymphatic vessels
Lymph node — a bean-shaped tissue made up of immune cells that filters lymph
Lymphatic system — the network of lymphatic vessels and lymph nodes through which lymph drains from tissues into the bloodstream
Lymphocyte — a type of immune cell
Prodrug — a medicine that only becomes active after entering the body once the active drug is released
You probably know how blood vessels in the cardiovascular system transport oxygen and other substances around the body, but are you aware of the lymphatic system? “The lymphatic system sits alongside the blood vessels in your body,” explains Professor Natalie Trevaskis, a pharmaceutical scientist at Monash University. “It consists of lymph nodes and lymphatic vessels which transport a clear fluid called lymph from tissues into the blood.” Natalie and her team are exploring how the lymphatic system could be harnessed for more effective drug delivery.
The weird and wonderful lymphatic system
The lymphatic system has three main functions in the body. It helps balance our bodily fluids by removing excess fluid and waste products from our tissues, it transports fats from the intestine to the blood, and it plays a key role in the immune system as immune cells, including lymphocytes, travel through lymphatic vessels and reside in lymph nodes.
But these are only the tip of the iceberg – recent research has uncovered a wide range of other important and diverse functions of the lymphatic system. “For example, lymphatic vessels have been shown to have an important role in clearing waste products from the brain, and their malfunction has been implicated in Alzheimer’s disease,” says Natalie. Other exciting discoveries indicate that the lymphatic system can help repair tissue following injury or disease. “After we break a bone or have a heart attack, the cells that line the lymphatic vessels release chemicals that help heal the damaged tissue. This process could be harnessed to develop new treatments that accelerate recovery.”
Natalie’s lab discovered the lymphatic system’s role in the development of type 2 diabetes. “When we eat an unhealthy diet, the lymphatic vessels that drain the intestines leak fluid into surrounding fatty tissues,” she explains. “These tissues become inflamed and contribute to the onset of diabetes.”
Understanding the many roles of the lymphatic system is essential for designing medicines that target the lymphatic system to manage or prevent disease.
The lymphatic system for drug delivery
Most medicines are delivered via the cardiovascular system – they enter our bloodstream either following an injection or by absorption from the intestines. The lymphatic system provides an alternative delivery pathway that could be more effective for a wide range of drugs. “We know that the lymphatic system plays a key role in immunity and many diseases,” says Natalie. “So, if we can deliver medicines directly into lymph, they can reach their targets more specifically.”
Natalie’s lab developed a system that delivers diabetes drugs directly into lymph, which proved much more effective than delivery into the bloodstream. “Vaccines are another strong candidate, as they work by instructing lymphocytes how to identify pathogens,” explains Natalie. “These vaccines are more effective when delivered directly to the lymph nodes.”
Getting drugs into the lymph
Reference
https://doi.org/10.33424/FUTURUM612
So, how can drugs be engineered to enter the lymphatic system rather than the bloodstream? “Delivery to lymph is actually very straightforward,” says Natalie. “Lymphatic vessels in tissues have large gaps between the cells that line them, while the cells that line blood vessels are tightly joined together.” This means that molecules of a large enough size can enter the lymphatic system but not the cardiovascular system. “We can achieve specific delivery to lymph through several pathways,” says Natalie. “Either the drug molecule itself can be large in size, or we can attach small drug molecules to large carriers.”
Attaching small drugs to lipids, for instance, means that once they reach the intestine, they will enter the lymphatic system in the same way as fats we eat. Then, when the lipid is metabolised by the body, it can release the active drug. This is known as a prodrug. “In my lab, formulations containing lipids are prepared by drug delivery experts who mix the components in certain ways, often with specific pressure or agitation to ensure they are the correct size,” Natalie says. “We then measure drug uptake into the lymphatic system using animal models.” Animal models are given the prodrug, and a delicate procedure is then used to collect their lymph and measure drug concentrations within it.
From creation to rollout
Once a drug is created, it is a long road to get it into clinical practice. “First, you need to have data that shows the drug is effective, how it is best delivered in the body, and how it is eliminated from the body to prevent accumulation,” says Natalie. “Then, the drug must enter toxicology studies to show it is safe.” Human clinical studies can then commence, beginning with small numbers of healthy volunteers. “The dosage might be increased incrementally to determine a maximum tolerated dose,” says Natalie. “From here, the medicine will be tested in increasingly larger groups of people, to show it is safe and effective.”
Natalie’s team began working on the lipid prodrug technology in 2009 and had enough evidence to file a patent in 2017. “The patent was licensed to a pharmaceutical company under a research and development deal to further progress the technology,” she says. “In 2024, the company spun out a second company to solely focus on developing this technology. Our lead medicine, a prodrug to treat anxiety and depression, is now in the final stages of clinical trials.” Thanks to the work of Natalie and her team, lymphatic drug delivery systems are bringing real benefits to healthcare.
Professor Natalie Trevaskis
Institute of Pharmaceutical Sciences, Monash University, Australia
Field of research: Pharmaceutical science
Research project: Developing novel drug delivery systems to target the lymphatic system
Funders: Advanced Research Project Agency Health (ARPA-H, USA); Australia NHMRC Synergy Grant; Australian Research Council (ARC) Discovery and Linkage projects; Medical Research Future Fund (MRFF, Australia); Moderna; Protagonist Therapeutics
About pharmaceutical science
Pharmaceutical science involves the development of new medicines, while the related fields of pharmacology and pharmacy deal with studying the effects of drugs on the body and dispensing medication, respectively.
Natalie began her career working as a clinical pharmacist in a small-town pharmacy, dispensing medicines to patients. “I enjoyed interacting with the community, but I wanted to contribute more to the world,” she says. “I felt this could be through developing new medicines, which is why I pursued a PhD in pharmaceutical science.” Natalie now runs her own lab, working with a diverse team (including chemists, biologists, clinicians and regulatory scientists) to develop new drugs to improve healthcare. “I love that our work can potentially change people’s lives for the better,” she says. “And I love working with people from many different backgrounds to collectively solve interesting challenges.”
In recent years, new technologies have made it possible to develop gigantic datasets. Natalie believes a big challenge for pharmaceutical scientists lies in working out how to use this data. “There could be a tendency to generate data without thinking about why,” she says. “I think the next generation will need to sit and think deeply about how to generate and process genuinely useful data.” Artificial intelligence (AI) is likely to be both a help and hindrance in this area. “Medicines are already being developed with AI assistance,” Natalie says. “Still, there is a strong need to use human intelligence to consider how our work can best help the world and nuanced ideas that AI could miss or neglect.”
Pathway from school to pharmaceutical science
Natalie recommends studying a wide range of subjects at school, to get as broad an education as possible. “Once you begin to specialise in pharmaceutical science at university, you lose the opportunity to study subjects like arts and drama,” she says. “But these subjects teach critical skills for scientists, such as creating graphics and public speaking.”
Undergraduate degrees in pharmaceutical science and related fields tend to require biology, chemistry and mathematics qualifications.
A range of undergraduate degrees can lead to a career in pharmaceutical science, including pharmaceutical science, pharmacology, pharmacy, biomedical science, molecular biology and chemistry.
While at school, Natalie attended Australia’s National Youth Science Forum (nysf.edu.au) which allowed her to visit universities.
The Faculty of Pharmacy and Pharmaceutical Sciences at Monash University runs outreach programmes for high school students: monash.edu/pharm/future/outreach
Explore careers in pharmaceutical science
A career in pharmaceutical science could involve developing or testing new drugs for a pharmaceutical company or at a research institution.
Monash University has a video about the difference between pharmacy and pharmaceutical science, and a quiz to help you decide which career is best for you: monash.edu/pharm/future/whats-the-difference-between-pharmacy-and-pharmaceutical-science
Reach out to labs that conduct research that interests you and ask whether they can host you as an intern or give you a tour of the lab.
Meet Sanjeevini
Dr Sanjeevini Babu Reddiar is a postdoctoral researcher in the Trevaskis Group at Monash University
As a teenager, I was fascinated by how the world works. I was drawn to the fundamentals underpinning everything, from the human body to physical theories. Coming from a family of Indian and Sri Lankan immigrants, I was strongly encouraged to pursue medicine, but through exposure to different fields, I found ways to carve my own path.
I grew up thinking I wasn’t creative. It wasn’t until university that I realised that creativity was also about noticing patterns others missed or approaching familiar problems in new ways. This fundamentally reshaped how I think and work.
I wanted to study something big and important. Pharmaceutical science seemed perfect – a field where I could explore fundamental biological questions while also developing life-changing interventions.
My days in the lab involve a mix of problem solving and collaboration. I do a lot of troubleshooting and developing analytical methods, as well as designing experiments, contributing to team discussions and helping to shape new research projects. I also co-chair HER Research Matters, a grassroots initiative committed to supporting women in STEM through networking, mentorship and advocacy.
Pharmaceutical science is an intellectually rich career that teaches patience, creativity and resilience. Beyond developing new therapies, it also advances our fundamental understanding of how our bodies work – uncovering insights that can transform medicine, public health and how we approach disease prevention.
In my free time, I’m a passionate reader. I read everything from science and history to philosophy and fiction. I also love hiking, playing tennis and travelling, and I have a soft spot for British murder mysteries!
Sanjeevini’s top tip
Be open to saying ‘yes’ – my career path was shaped less by a single ‘aha’ moment and more by a pattern of saying ‘yes’ to opportunities that sparked my curiosity. You won’t know what energises you until you try.
Meet Mohammad
Dr Mohammad Abdallah is a postdoctoral researcher in the Trevaskis Group at Monash University
As a teenager, I spent most of my time playing soccer. I played it anywhere and everywhere, regardless of the weather. When I wasn’t playing soccer, I was watching it at home on the TV.
Before I started my PhD, I worked as a clinical pharmacist in a hospital intensive care unit. My responsibilities included monitoring patients’ responses to drugs, adjusting dosages and conducting research to address gaps in disease management. I decided to develop my research skills by joining a PhD research project specialising in pharmaceutics – the area of pharmaceutical science focused on the design and optimisation of new drugs and their administration to patients.
I’m involved in many research projects in Natalie’s lab. I focus on novel drugs to target the lymphatic system, and how they interact with proteins, lipids and cells. Any disturbance in the function or structure of the lymphatic system can cause disease, so these drugs can lead to optimised treatment of lymph-related diseases.
There is no typical day in my role. My tasks include reading scientific literature, designing experiments, conducting studies on lab animals, testing samples, teaching research students on research methods and presenting data. Often, new data changes the direction of our next research plans.
Pharmaceutical science aims to improve patients’ outcomes. The people in our communities – family, friends, neighbours – could be helped by our work. I feel huge satisfaction when we make discoveries that can enhance people’s quality of life.
In my free time, I enjoy hiking in nature and wildlife photography. I also love cooking – my friends say I’m an excellent chef!
Mohammad’s top tip
Follow your passion to achieve your dreams. Don’t be discouraged by any bumps along the way – patience and persistence will help you face challenges.
Do you have a question for the team?
Write it in the comments box below and the team will get back to you. (Remember, researchers are very busy people, so you may have to wait a few days.)
Discover how pharmaceutical scientists are reducing the side effects of chemotherapy:
futurumcareers.com/exploiting-an-immune-response-to-alter-the-side-effects-of-cancer-treatment
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