Microbubble Enhanced Imaging and Therapeutic Delivery

1st July 2017 to 30th June 2020

Our Programme of research addresses several key challenges that need to be resolved to allow the clinical development of MBs as combined therapy and diagnostic agents. In our recent EPSRC Programme we succeeded in building an instrument for the manufacture of MBs (that have a targeting agent and conjugated drug payload). This enabled us to test their ability to target cancer cells and to effectively treat tumours in pre-clinical models. In order to progress our MBs to the point where they could be used for first-in-man trials we need to satisfy regulatory agencies that our MBs are safe, and have clear clinical benefit. We will also need to demonstrate that they are cost effective, if providers are eventually to take- up this treatment modality.

We have developed a two-pronged approach to developing microbubbles for drug based delivery: 1) Many drugs fail to reach clinical trials because, whilst they are potent as drugs, they are difficult to deliver into cells, or tissue because of poor solubility or becasue they are too toxic to use. For this we propose to develop a new integrated screening platform, that will use the combination of MB+ultrasound, for aiding the delivery of such drugs into cells (and tumour models). This will not only allow re-assessment of many existing drugs but will also speed up the screening of new drugs. Through partnership with the Medicines Discovery Catapult we will promote uptake of this technology with pharmaceutical companies and thereby reduce cost for the identification of new drug candidates.

2) We will develop our, patented, MB production instrument to the point where it could be manufactured by an external company for the first-in-human trials. As part of this we need to optimise how we make the MBs, modify how the drugs and targeting agents are linked to each other and address issues such as ease of use, sterility etc. We also need to show that we can eliminate tumours completely using our MB+US approach. By using materials that have been manufactured according to specific standards (GMP), that are suitable for clinical trials, and processes that are in accord with Good Laboratory Practice we will undertake the necessary in-vitro and in-vivo testing required for moving this “Investigational Medicinal Product” to Phase 1 (First in Human) Clinical trials.

Hydrophobic Drug Delivery

1st April 2013 to 31st March 2016

This project is focused around the research of Microbubbles for Hydrophobic Drug Delivery and Enhanced Diagnostics. This will be used for personalised healthcare for the treatment of Colorectal Cancer, commonly referred to as Bowel Cancer. Professor Steve Evans, University of Leeds, School of Physics and Astronomy is leading the project.

Engineering Therapeutic Microbubbles

EPSRC funded – Sept 2010 – Feb 2014

Colorectal Cancer (CRC) is the third most common cancer in the UK, with approximately 32,300 new cases diagnosed and 14,000 deaths in England and Wales each year. Occurrence of colorectal cancer is strongly related to age, with 83% of cases arising in people older than 60 years. It is anticipated that as our elderly population increases, CRC will increase in prevalence (National Institute for Clinical Excellence, raises important questions relating to treatment in elderly patients balanced with quality-of-life and health economics considerations.

The challenge to nanotechnology and engineering is to deliver cost-effective, less invasive treatments with fewer side-effects and potential benefits for quality of life in patients. This is particularly important in CRC at the present time as the NHS bowel-screening programme is rolled out for all individuals aged 60 to 69. This raises important issues for rapid, accurate, and acceptable, safe and cost-effective investigation and treatment of older symptomatic patients.

Ultrasound has a clear and growing role in modern medicine and there is increasing demand for the introduction of ultrasound contrast agents such as microbubbles (MBs). These MBs are typically less than one hundredth of a millimetre in size, so that they can pass through the vasculature, and lead to imaging enhancements by scattering of the ultrasound signal. So-called “third generation” MBs will not only perform functional imaging with greatly enhanced sensitivity and specificity but will also carry therapeutic payloads for treatment or gene therapy. These will most likely be released by destroying the bubbles at the targeted site and their effect enhanced further by sonoporation (sound induced rupture of the cell walls to allow drugs in). Although the focus of our proposal is therapeutic delivery for cancer treatment, the basic technologies for MB development and ultrasound technology are equally applicable to other conditions e.g. cardiovascular and musculoskeletal disease where there is an unmet clinical need, particularly in ageing populations. As such this is a generic technology development relevant to different diseases.