Improved access to state-of-the-art and affordable medical care - especially in oncology and cardiology - is vital to ensuring that Europe’s ageing population is capable of taking care of itself in the future. New therapeutic options, such as externally triggered local drug release, represent one promising route currently being explored by researchers.
Around 50% of patients diagnosed with cancer undergo chemotherapy to treat their disease. Chemotherapy drugs flow through the bloodstream in search of rapidly dividing cells like cancer cells. But, in their quest to fight disease, these potent drugs end up attacking normal, healthy dividing cells, which leads to undesirable side effects. A targeted delivery method could be one way to tackle this issue.
This is the objective of the European Union-funded ’Image-controlled ultrasound-induced drug delivery‘ project (Sonodrugs). According to the researchers working on the project, nanomedicine, which is the application of nanomaterials and nanotechnology to health care, can lead to cost-effective treatments with fewer side effects, less burden on the patient and faster recovery time.
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"Sonodrugs is addressing clinical needs by developing novel drug-delivery technologies for localised treatment of cancer and cardiovascular disease," explained project co-ordinator Charles Sio of Philips Research Europe, Eindhoven, the Netherlands. "It's developing innovative concepts where drug release can be triggered by focused ultrasound-induced pressure or temperature stimuli within the diseased tissue."
To achieve this, new drug-loaded nanocarriers are being designed for tailored drug-delivery systems that respond to either of these two stimuli. Magnetic resonance imaging and ultrasound imaging will then be used to guide, follow and quantify the drug delivery process, at the nanoscopic level.
"Following research on a broad range of materials and drugs, two nanocarriers have ultimately been selected, optimised and evaluated in combination with image-guided delivery tools and methods," according to Dr Sio. "The aim is to bring a promising new therapy option forward."
DRUG-DELIVERY INNOVATION
The potential benefits are tremendous - locally triggered release increases the delivery of drugs to the sites in the body where they are needed, increasing the effectiveness of the drug in attacking the disease while decreasing the body’s exposure to possible toxicity and related side effects.
This highly interdisciplinary project, which was completed late last year, combined chemistry and engineering technology, diagnosis and therapy, and called on the expertise of academic partners, university hospitals, small and medium-sized enterprises and large industry. Co-ordinated in the Netherlands, other countries involved in the research included Belgium, Cyprus, France, Germany, Finland, Italy and the UK. The EU contributed € 10,783,900 to the overall project cost of €15,903,800.
The project has resulted in eight patents on nanocarriers, hardware and methods, some 36 publications in high-ranking journals and over 100 presentations at international conferences. During the course of the project, three PhD trajectories have been finished successfully, two PhD theses are in preparation and at least five more are in the pipeline.
Dr Klazina Kooiman, of the Erasmus Medical Centre in Rotterdam, the Netherlands, was one such student. Her PhD project revealed that micro gas bubbles can help drugs used to treat cardiovascular diseases and cancer to work better by injecting the bubbles into the body - and allowing them to massage the cell walls. This improves the cells’ ability to absorb the drugs.
Drugs used to treat cardiovascular diseases and cancer do not work optimally because many cells have difficulty admitting the drugs. The cell walls are difficult to penetrate. Dr Kooiman wanted to stimulate the cells in such a way that they would open up. In the laboratory, she released micro gas bubbles into trays with cultured cells and she made the bubbles vibrate using sound waves. “It was as if they were dancing along the cell walls, thereby massaging them. As a result, it appeared that the cells became more permeable,” according to the researcher.
The cells allow more drugs through when the bubbles pulsate harder and 'dance'. “The tests with the micro bubbles were captured using a high-speed camera that can record millions of images per second. It also shows that the cells withstood the vibrations," explained Dr Kooiman. "It's possible, therefore, to perform this method without damaging healthy cells.”
Kooiman sees a bright future for the ‘dancing bubbles’, particularly because the bubbles can also be filled with drugs and made in such a way that they only adhere to sick cells. “This means that drugs can be administered locally in a body. Drugs can then be administered locally in high doses but, at the same time, limiting side effects because the drugs are no longer present in the entire body.”
NOVEL TREATMENT METHODS
It will take some years before the gas bubbles can be used on patients. Further research is necessary to determine the frequency of sound waves to be used and the best combination of drugs and gas bubbles. But the first tests are promising.
Thanks to the team’s dedicated work - both fundamental research and applied science - significant advancements have been made in the development of novel treatment methods. A body of knowledge has been built up, and young European scientists are now experts in this field. This increases the potential for health-care innovations by European academic institutions, hospitals, and industries, backed by patents on several key findings.
"Our concepts have been successfully tested in preclinical studies for the delivery of the anti-cancer drug doxorubicin and RNA-based compounds against cardiovascular diseases," explained Dr Sio. "Extrapolating these results, the platform can potentially be used for many different drugs, providing opportunities for European pharmaceutical companies."
Perhaps more importantly, however, patients may have access to treatments with higher efficacy and fewer side effects, which may improve their quality of life and reduce the debilitating effects of these dreadful diseases. What is more, doctors may have access to new treatment methods and, overall, the costs to society of the disease may decrease.