Getting therapeutics to their site of action in the body is a key step in successful treatment. Claire O’Connell talked to Prof Sally-Ann Cryan about her work to deliver the therapeutic goods.
How do you get a therapeutic agent, like a drug or gene or cell, to where it needs to go in the body? That’s something Prof Sally-Ann Cryan spends a lot of time pondering. Because a new therapy may look fantastic on paper and in the lab, but unless it can get to its site of action in the body at the appropriate dose, it might as well not be there.
“What I do is translational and molecular pharmaceutics, and that is about enabling the new molecules to get to the clinic, particularly where we are dealing with ‘difficult-to-deliver’ cargoes in the body,” explains Cryan, who is an associate professor of pharmaceutics in the School of Pharmacy at the Royal College of Surgeons in Ireland (RCSI).
Breathing new drugs into life
A graduate of pharmacy from Trinity College Dublin, Cryan had early experience in dispensing to patients with lung conditions and she has asthma herself. Both helped to pique her interest in delivering drugs into the lungs, and this a major theme in her research, which receives support through various funders, including the Irish Research Council and the Health Research Board.
Over the last decade, changes in the drugs and therapies that people are now looking to deliver into the lungs, and the advent of biologic drugs, has opened up new challenges.
“A lot of the current inhalers on the market are delivering small molecule drugs which are extremely potent at that site and that is the way they work, you don’t need a very efficient delivery system,” she explains. “The problem when we come into the new era of biotech molecules is that, for many of them, to be effective they must reach a specific site or target within a particular type of cell. They may also need to get down into the lower part of the lungs, and that’s not easy because of the complex anatomy there.”
The demand has driven a surge of innovation both in engineering new inhalers and also in developing new ways of formulating the drugs and enhancing delivery, says Cryan. She is now working on lung-based delivery platforms for various lung and systemic diseases and current projects in her lab are looking to tackle infection, such as tuberculosis, and inflammation in chronic conditions, such as cystic fibrosis and chronic obstructive pulmonary disease (or COPD).
In many cases, sneaking the therapy into the lungs involves linking the biotech drug to a polymer, or coating it with a polymer capsule to carry it into the lungs and target it to the appropriate site of action. “We look at advanced polymeric systems and we also work with chemists to develop completely new polymers and materials,” says Cryan.
Academia and industry in the mix
In addition to looking at drug delivery in the lungs, Cryan is also an investigator in the Tissue Engineering Research Group at RCSI, led by Prof Fergal O’Brien, where she focuses on how agents, such as growth factors, can be released from scaffolds implanted into the body to help bone to regenerate. She is also working on an academic-industrial EU-funded project with Dr Andreas Heise at Dublin City University to investigate new hydrogels in drug delivery. She also has several industry collaborations, including a long working relationship with Galway-based Aerogen.
Cryan has seen a “seismic change” in how drug-delivery research is now being carried out in Ireland, with a number of new academic Schools of Pharmacy and research clusters, such as the Science Foundation Ireland-funded Irish Drug Delivery Network bringing academia and industry together.
“I work with academics and clinicians who have molecules, proteins or genes or cells they want to have delivered, and I also work with pharmaceutical and medical device companies,” she says. “And the big area now is convergent technology, where you are putting therapeutics together with medical devices and often using a material to enable that. We are at that interface where we can provide the know-how on what material to use, how to put that together and formulate it with a drug molecule so you can target your drug or use your device more effectively.”
Found in translation
But there are still challenges, and Cryan sees the big thrust now in developing more appropriate models to develop drugs for human use.
“There’s a lot that’s getting lost in translation – medicines are getting so far into the development process but then failing when they go into a human, and we are losing them because of models that don’t really mimic humans,” she explains. “But there’s a lot of fundamental research we can do to develop better tissue models, including diseased tissue in vitro. So we are trying to develop three-dimensional models of parts of the lung so we can check for toxicity and efficacy using human cells that can cross-talk to each other as they might in the body. Both in Ireland and on a more global scale you have pharmaceutical scientists, tissue engineers and cell biologists working together to try and come up with these kinds of models.”
Cryan believes Ireland now has the enabling technologies to do well in drug delivery and research to improve translation of therapeutics to the clinic.
“Convergence is the big trend, bringing the aspects together – we have advances in biomedical research where we understand disease and the sites of disease better and we have new therapeutic options emerging to treat them,” she says. “It is about putting those together so we have the right therapeutics with the right materials and the right devices for delivery. Ireland has a lot of expertise in these areas, this is something we should be able to do well.”
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