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

10 25 50
 
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