A new nano particulate vehicle for ultrasound enhanced delivery of Cisplatin

Chemotherapy for the treatment of cancer continues to make great advances. However the current methods of drug delivery rely on injection into a blood vessel and remain very poorly optimised if at all. This results in having to administer high levels of the drug to the whole body, to give local concentrations in the tumour that are effective in reducing or eliminating the tumour. What this means for the patient is significant side effects such as general debilitation, but also the compounds used can be toxic to the kidneys, liver and nerve tissues. One such compound used is called Cisplatin and is the drug of choice for the treatment of head and neck cancers, which have an unacceptably high mortality rate of over 50%. This high mortality rate is due to a number of factors but one of the main factors is that these particular tumour types are quite aggressive and difficult to treat. Thus to develop a delivery system that gives much higher drug concentrations where it is needed would have significant benefits for both the patient and the healthcare provider. One method to deliver drugs to tumours is to utilise nanoparticles. The reason this potentially can be effective is that blood vessels in tumours are "leaky" and will allow nanoparticles to cross from the blood vessel into the tumour. However even though the nanoparticles cross the blood vessel, the particles can show quite poor uptake by the cancer cells. Thus our system aims to combine a nanoparticle within a microbubble. The idea behind the delivery system is that the nanoparticle trapped within the microbubble are injected and an ultrasound probe is applied to the site of the tumour. As the particles passes beneath the ultrasound probe, the ultrasound bursts the bubble and this produces a small shock wave and this has the effect of forcing the nanoparticle across the blood vessel wall and forcing the particle into the cells of the surrounding tumour. This ultimately will give much more localised delivery of the compound meaning enhanced efficacy and reduced side effects for the patient.

The primary group who will benefit from this work will be patients who are afflicted by oral cancer. This is particularly important, as, whilst the patient numbers are not high, the mortality rate is at an unacceptable high level of over 40% worldwide. Treatment for this disease can also require radical surgery with a poor prognosis for the patient and a significant cost burden for the healthcare providers. Therapies are continually improving and the drugs used are effective, but could be made much more effective, with reduced side effects if we could target the therapy. Thus the patients will benefit by having a much more effective treatment, with reduced side effects and improved long term outcomes.
The work will also have an impact on healthcare providers as the administration of the therapy is simple to administer and also to trigger the release using ultrasound. With improved targeting there will be a reduction in the number of cycles of treatment needed, which will free up staff and with the targeted delivery a reduction in the debilitating side effects, which need to be treated, both short term (nausea) and long term (potential nephro- and neurotoxicity).

From a commercial perspective, this technology is not only applicable to Cisplatin but also to other compounds such as Doxorubicin and also for the localised targeting of antibiotics and thus there is a high impact to be gained within industry to develop this technology not only for cancer therapeutics as a first target but also for a much wider range of clinical problems. It may be that we have the opportunity to close multiple licensing deals with a number of companies in different clinical areas.

The technology we aim to develop also is base don a simple to understand concept and this offers and opportunity to achieve impact as a demonstration to schools, to encourage schoolchildren to become interested and excited about the research fields of bioengineering and the possibilities available. One of the particularly rewarding aspects for the applicants is to be involved with the development of products that can have a direct positive impact on peoples lives and we hope to convey this to the next generation of innovators.