Engineering Virus-like Nanoparticles for Targeting the Central Nervous System
Lead Research Organisation:
University of Sheffield
Department Name: Materials Science and Engineering
Abstract
Despite vast efforts that have been made to develop novel strategies to overcome obstacles, the delivery of any therapeutic agents to central nervous system (CNS) is still a major challenge. This must be overcome to develop fully effective treatments for conditions affecting it, from dementia to motor disorders. The most limiting factors to deliver therapeutic agents to the CNS are the barriers that protect it: the blood brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB). We seek to use polymer nanotechnology to engineer biocompatible and nanometer-sized vectors that are able to pass through different extracellular and biological barriers, opening up the possibility of selectively targeting potentially effective treatments to where they are needed. We will combine recent advances in both polymer nanotechnology and neuroscience implementing experimental design and biological evaluation with whole body imaging techniques and modelling approaches. Targeted delivery of therapeutic agents direct into the CNS has the potential to cut down on debilitating side effects associated with current treatments and minimize neuronal damage in CNS degenerative disorders, both of which have major implications for life long health and well being for both patients and carers. Our long term aim is to demonstrate the potential of this technology in the clinic using the example of motor neuron disease where members of the team have excellent combined scientific and clinical expertise. We plan to interface Chemistry, Physics, Bioengineering with Clinical Neuroscience and Neurology. This will allow the bridging of novel scientific discoveries into real world medical applications through rigorous engineering characterization. This is a very challenging and strategic project. Yet, achieving the objectives presented would be very valuable in validating a novel biomedical delivery system ready for clinical studies with the potential to effectively treat several neurological disorders. In the first 2 years will focus our effort on two specific exemplar disorders. Therapies which show efficacy in those could potentially be extended for other common neurological disorders such as Parkinson's and Alzheimer's diseases. By the end of the three years, we aim to identify at least one delivery mechanism that has efficacy data for one disease/target in a preclinical model. In order to realize this effectively we will engage with patient groups and the general public throughout the process, stimulating interest, managing expectations, addressing ethical and safety concerns and the regulatory agenda. So as to facilitate any potential clinical evaluation we also aim to engage from the early stages of the programme with the Medicines and Healthcare products Regulatory Agency (MHRA), and clinicians and patient groups. Finally we will liaise with technology transfer and business managers and integrate the multidisciplinary training including companies that have already established collaborations with our team such as: Biocompatibles Ltd, Oxford BioMedica Ltd, GlaxoSmithKline, and UCB Pharma.
Publications
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in ACS central science
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in Scientific reports
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Polymersomes-mediated siRNA delivery for states of hormone excess
in Endocrine Abstracts
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in Scientific reports
| Description | JE-s form includes all the outcomes |
| Exploitation Route | Our papers published out of these work have been highly cited. Several groups are now adopting the same strategy to engineering nanoparticles |
| Sectors | Chemicals,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
| Description | This work has now allowed us to become one of the group very active in drug delivery to the CNS |
| First Year Of Impact | 2012 |
| Sector | Chemicals,Healthcare,Pharmaceuticals and Medical Biotechnology |
| Impact Types | Societal,Economic |
| Description | Biocompatible Polymer Colloids for Bionanotechnology Applications |
| Amount | £1,226,426 (GBP) |
| Funding ID | EP/J007846/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 11/2011 |
| End | 10/2016 |
| Description | Development and intracellular delivery of probes for super-resolution microscopy |
| Amount | £50,000 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2014 |
| End | 08/2015 |
| Description | Evaluation of intracellular trafficking of non-viral gene delivery vectors |
| Amount | £72,765 (GBP) |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 10/2014 |
| End | 09/2017 |
| Description | Magnetic resonance and matrix-assisted laser desorption mass spectrometry imaging (MRI and MALDI-MSI) for progressing the development of tumour vascular-targeted drugs |
| Amount | £2,396,540 (GBP) |
| Funding ID | CRUK/EPSRC Cancer Imaging Programme Grant |
| Organisation | Cancer Research UK |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 01/2009 |
| End | 12/2012 |
| Description | Molecular Engineering of Virus-like Carriers |
| Amount | € 1,643,736 (EUR) |
| Funding ID | ERC-STG-MEVIC |
| Organisation | European Research Council (ERC) |
| Sector | Public |
| Country | Belgium |
| Start | 10/2011 |
| End | 09/2016 |
| Description | Polymersome for airway delivery |
| Amount | £79,561 (GBP) |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2013 |
| End | 09/2017 |
| Description | Biocompatibles UK Ltd |
| Organisation | BTG |
| Department | Biocompatibles |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | We have had 1 PDRA and 2 PhD project sponsored by this company as well as to establish a EPSRC Partnership |
| Collaborator Contribution | Commercialisation and technology transfer |
| Impact | Commercial product CeLluminate sold for two years (now due to company restructuring, the product is not longer sold) |
| Start Year | 2007 |
| Description | PhD studentship on intracellular delivery |
| Organisation | AstraZeneca |
| Department | Astra Zeneca |
| Country | United States |
| Sector | Private |
| PI Contribution | Collaborative project on studying new gene delivery vectors |
| Collaborator Contribution | Intellectual and in kind |
| Impact | just started |
| Start Year | 2014 |
| Description | Polymersomes for airways delivery |
| Organisation | Vectura Ltd |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | We are translating our technology to aerosol and nebulising delivery method to explore new way to asses human airway delivery |
| Collaborator Contribution | not yet but soon we will access expertise and facilities to develop airway delivery methods |
| Impact | not yet |
| Start Year | 2013 |