Long acting nanocomposite materials for parenteral delivery with a focus on intrathecal delivery

Intrathecal administration is a route of drug delivery via an injection into the subarachnoid space so that it reaches the cerebrospinal fluid (CSF) and is used in chemotherapy, or pain management. Utilising this mode of drug delivery allows delivery of therapeutic concentrations directly to the site of action, whilst avoiding systemic toxicity elsewhere in the body. To date there are very few controlled release formulations for intrathecal delivery in pain management or chemotherapy. Considerable progress in the development of low molecular weight hydrogel makes these appealing materials for designing controlled-release drug delivery systems. The inclusion/incorporation of nanoparticles in three-dimensional nanofiber structures is a novel way to obtain multicomponent systems with diverse functionality. Our project will develop novel nanocomposite materials that can be injected intrathecally into the subarachnoid space to allow the controlled release of nanoparticles and that could also penetrate CNS tissues including the CSF -brain barrier. We will develop a nanocomposite material of nanocapsules and a low molecular weight hydrogel that is appropriate for intrathecal delivery. The nanocapsules will be designed to be small enough to penetrate brain tissue(1) ie. approximately 50 nm and potentially the pia mater, dura mater and the cerebral spinal fluid (CSF) -brain barrier. In addition, the hydrogel is a "soft" injectable, self -healing material that will minimally disrupt pressures and flow of the CSF(2).

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.