Novel formulations for spraying therapeutic cells for CNS injury

The goal of this project is to develop a spray device and hydrogel formulation combination for the delivery of therapeutic cells (e.g human neural stem cells, MSCs, or cells derived from human induced pluripotent stem cell) for brain injury. This combination will allow optimal delivery and location of the therapeutic cells onto the brain parenchyma at the time of surgery. The spray device and formulation will be designed to ensure intimate contact of the therapeutic cells with the brain parenchyma.

We will use an airbrush design to spray the therapeutic cells in the hydrogel formulation from in-situ forming physical gels, chemically cross-linked gels and extra cellular matrix (ECM) gels derived from CNS tissue. This project fits the research themes of EPSRC CDT in Advanced Therapeutics and Nanomedicine of systems pharmaceutics and novel materials and processes.

The project will be divided into four work-packages and deliverables as follows:-
(i) To assess cell viability from a simple spray device and select a hydrogel formulation and therapeutic cell type. Deliverables: selection of suitable hydrogel formulation (s) and relevant cells for progression.
(ii) To optimise the spray parameters for a novel device and hydrogel formulation. Deliverables: Operating conditions for spraying pectin solution, cross-linked polymers or ECM derived hydrogels with the bespoke device to be able to create a spray with different droplet sizes and velocities to test in (iii) and (iv).
(iii) To measure cell adherence and location on brain parenchyma when sprayed from a novel device in a hydrogel formulation. Deliverables: spray parameters and hydrogel formulation defined for location of the cells on the brain parenchyma.
(iv) To assess cell viability of therapeutic cells from an optimised hydrogel formulation and spray device parameters. Deliverables: optimised hydrogel formulation, therapeutic cell type and spray parameters)

Society needs better medicines and requires scientists trained in new ways to develop these therapies towards the clinic. The pharmaceutical industry demands a culture change in research training to equip the next generation of leaders with the breadth of skills to translate the most innovative scientific concepts. The proposed CDT will deliver these leading scientists, highly-trained in interdisciplinary areas central to the EPSRC Healthcare Technologies priority whilst at the same time generating high impact research data and exploitable results. These outputs will benefit the Pharmaceutical sector, both 'big pharma' and SMEs, as well as underpinning key advances central to EPSRC Themes in Healthcare Technologies such as Diagnostics, Therapeutics and Medicines. Partners in the proposed CDT, including three of the world's largest pharmaceutical companies, have helped to shape this proposal to ensure maximum relevance in a time of rapid change in the industry.
The CDT will specifically address a key need, highlighted by the Association of British Pharmaceutical Industries' (APBI) to reverse 'the decline in skills among young people training for careers in science (which) has a serious effect on the development of a knowledge-based industry'. Impact for university and industry partners also includes generation of IP-protected product opportunities. We anticipate a number of new patent application filings to cover inventions in high throughput material selection, self-assembled drug carriers, engineered in vitro models of diseased tissue, and new properties and therapeutic outcomes of specifically formulated biotherapeutics.
By building multisite, multidisciplinary teams through translation-focused collaborative projects, the CDT will further advance mutual benefits to industry and UK society. In 2007, the Gross Value Added (GVA) contribution per employee within the pharmaceutical industry (£233,000) was ~ 3.5 times than the GVA of other high-tech sectors in the UK. Scientists and engineers comprise 42 % of the pharma workforce, indicating clear economic impacts of high-level PhD training in this area. Transfer of knowledge and technology into the Healthcare sector, enhances treatment options and quality of life for patients and carers. Improvements in pharmaceutical science and enhanced academy / industry pathways to translation are important across many other industry sectors: the UK market for formulated products is worth around £180bn a year, with a potential in emerging overseas markets of around £1,000bn (Chemistry Innovation KTN Strategy Report 2010).
Impact beyond the industry sector is expected via outreach activities and engagement of CDT students and staff, in for example, After-Schools clubs and media activities. The subject base for the proposed Centre i.e. Nanomedicines, and the link between academic and industry partners, offers many opportunities for positive public engagement. The applicants have a track record, (e.g. in the award-winning 'Test-Tube' web videos), of showing how pharmaceutical science is pivotal to the development of new medical breakthroughs. Highly motivated and enthusiastic CDT students have demonstrated, (e.g. at EPSRC Showcase events) that their training enables them to be powerful ambassadors for their universities, industry partners and EPSRC.
Impact activities will be embedded throughout the CDT via continual training, monitored via IP and Knowledge Transfer Review meetings of the CDT Steering Group and Advisory Boards, and further encouraged through consultation with Outreach and Impact Champions appointed in Nottingham and UCL as part of EPSRC Impact Acceleration Accounts (IAA). Prof Alexander is Academic Lead for the IAA in Nottingham and so is well-placed to encourage impact activities in the CDT.
The longer-term impact of the CDT will be a sustainable future for the the UK pharmaceutical science base, leading in turn to wider healthcare and societal gains.