Development of mechanisms to increase the efficacy of clinical drug delivery to brain metastases

Lead Research Organisation: University of Oxford
Department Name: Engineering Science

Abstract

I am continuing work that I began in my 4th year Master's Research Project by working in a multi-disciplinary team in BUBBL in the IBME to develop a novel method of delivering drugs non-invasively to incredibly localised regions in the body for use in treatments such as chemotherapy. The treatment methodology that I am working towards uses nanodroplets - nano-scale spheres of liquid polymer containing a small amount of maghemite. The droplets can be further specialised by being made to contain a desired drug. The maghemite allows the droplets to be held stationary at a target site inside the body, for example, a tumour, using a large magnetic field placed outside of the body. As the boiling point of these droplets is only slightly above body temperature, the droplets will boil and expand rapidly when exposed to ultrasound of sufficient intensity, forcing the drug into the cells nearby. The force of this expansion can be closely controlled by the frequency and pressure of the ultrasound. This localisation allows for much higher doses of delivery of drug to the target site than the systemic delivery that is currently used. It will also deliver much lower side effects because any droplets not delivered to the target site will be excreted. This is especially important in treatments such as chemotherapy.
The specific focus of my project will be to apply these developing new technologies to tackle brain metastases - small tumours that spread via the blood and lymph system from a primary tumour and then lodge in the brain. To treat brain metastases, we plan to use chemical targeting - it is possible to coat the droplets in proteins that chemically bind to tumour cells or cells that are close to tumours. Magnets can be used to slow the flow of droplets past target areas, allowing sufficient time for this chemical bond to be formed. The magnet is then removed entirely from the patient, and those droplets which have not bound to cells flow out of the brain and are excreted. Using this method, it should be possible to drastically increase the amount of drug delivered to the tumours, even those too small to image, while reducing the side effects on the patients. I am working within the Oxford Centre for Drug Delivery Devices team to prepare this technology for clinical trial.
This technology has an incredible potential to improve the lives of so many patients - it is cheap, it can be easily expanded to different treatments, and most importantly it is non-invasive and exposes patients to a much lower level of risk than existing treatments. Areas of particular interest to me include combining the technology with automatic medical scan analysis, improving our understanding of the effect of ultrasound on cells and fully developing magnets and devices that are optimised for different areas around the body.

This project falls within the EPSRC Healthcare Technologies research area. At present, there are no companies or collaborators involved with my project specifically. This is not true for the research group that I am working within.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/N509711/1 01/10/2016 30/09/2021
1798447 Studentship EP/N509711/1 01/10/2016 30/09/2020 Oliver Vince
 
Description More effective microbubbles at delivering therapy to brain tumours.
Exploitation Route Development of clinical technologies for the treatment of brain cancer.
Sectors Pharmaceuticals and Medical Biotechnology

 
Description Outreach events and development of technologies that will hopefully improve brain cancer treatment in the future
First Year Of Impact 2018
Sector Pharmaceuticals and Medical Biotechnology