We are developing better methods for drug delivery. Currently most drugs for most diseases are given by mouth or by injection. The problem with that is that they go everywhere in the body and a very small percentage does what it is supposed to do. Most of it manifests itself as side effects, or gets flushed out of the system.
We’re developing vehicles – bubbles specifically – to encapsulate drugs so they are inactive until they reach the target site. We want to get as many as possible in the target region, and then trigger their release.
To do this, we are using ultrasound because it’s very low risk, very convenient for doctors and patients, cheap and seems to be extremely effective. We also use magnetic fields to get the bubbles to the target area. Because ultrasound and magnetic fields can be applied from outside the body, they are a very good way of getting the drugs to where they need to go.
The core of the bubbles is a relatively insoluble and non-toxic gas. This means the bubbles are fairly stable, they don’t dissolve away too quickly. To coat the bubble we typically use proteins and other surfactants which are naturally found in the body. We also use biopolymers but they produce bubbles that are less responsive to ultrasound. Ultimately the gas leaves the body via the lungs and any waste material from the coating will be excreted via the liver or kidneys.
This treatment has potential applications in cancer, stroke, and infections. The general principles are applicable to other diseases too. We’re looking mainly at abdominal cancers: liver, kidney, and pancreas; the third particularly as there are currently very few solutions for pancreatic cancer.
The two areas where ultrasound is not great are the lungs which are full of gas, and bone because it is a very solid interface. We are however running a research project looking at the treatment of brain cancer as part of a major programme grant, between the Department of Engineering Science and the Department of Oncology. The challenge is to extend people’s period of survival and ultimately cure cancer. It irritates me intensely when people say someone has been cured, when all that’s happened is that their life has been extended by six months and their quality of life is often very poor. We need to see a ten or twenty year extension.
I’m also working on antibiotic delivery: encapsulating antibiotics in polymer capsules. These are embedded in the bladder to release slowly over time so you get a more concentrated dose just in the infected region, and not throughout the body.
There’s a huge problem with chronic urinary tract infections particularly in the elderly. It’s strongly associated with dementia but widely ignored. We’ve been working with clinicians at the Whittington and Royal Free Hospitals in London on this. They know that if they can give a sufficiently high dose they can clear the infection but obviously you can’t give someone who already isn’t very well a massive dose of antibiotics. It’s likely to actually make things worse.
We need to stop prescribing antibiotics so frequently. We need to keep them for serious infections where they are desperately needed as a last line of defence, not just to keep people quiet if they’ve got a cough. We’re already seeing resistance to antibiotics. We’re preventing a very effective drug from being useful.
We also have some really exciting work going on in collaboration with the University of Ulster and colleagues in Oncology trying to deliver oxygen. The problem with lots of cancer treatments is that the tissue you’re trying to treat has become starved of oxygen and that makes the treatment less effective. We’re trying to pre-prime it with oxygen so that the subsequent chemotherapy, radiotherapy or other treatment will be able to work.
There are four of us in our group, including myself and Professors Coussios, Cleveland and Carlisle. Between us we have 40-50 researchers. Our research is funded by EPSRC, Wellcome Trust, Leverhulme Trust, 1851 Commission, Cancer Research UK, and the Royal Society. I’ve also recently received an award from the Institute of Engineering Technology. The facilities in the Oxford Institute of Biomedical Engineering are wonderful. It’s great working with a hugely diverse range of people from mathematicians to clinicians.
With regards to clinical trials and using the findings of our research to treat patients, Oxford has been treating patients with therapeutic ultrasound for at least 15 years. Professor Coussios has a clinical trial running now using an existing drug with the current clinical ultrasound system. If the results are positive we very much hope this will pave the way for translation of the work we’re currently doing in the laboratory. We hope the antibiotic research will be in clinical trial soon. However, NHS take-up is probably another five years away at least.