POLYMER NANOMEDICINE: ENHANCING THE TRANSLATION FROM THE LAB TO THE CLINIC

Lead Research Organisation: University of Sheffield
Department Name: Biomedical Science

Abstract

There is a necessity to speed up the process of design, optimization and evaluation of formulation for biomedical applications. Such a process is even more crucial when it comes to the engineering novel nanometer-sized particles that can deliver therapeutic agents across the different barrier targeting only the damaged sites. Today such effort collectively known as Nanomedicine, is revolutionizing traditional therapy and enabling completely new therapeutic and diagnostic approaches. Nanomedicine is a multifaceted discipline that involves physicists, chemists, engineers, biologists and clinicians. This interdisciplinary nature is possibly nanomedicine greatest strength and greatest weakness at the same time. Indeed while this allows a more complete understanding of the different physico-chemical aspects as well as the biological implications, often the methodologies and the approaches are substantially different across the different disciplines hindering the validation and the fast translation of the final results. Herein we propose a rigorous approach of synthesis and pre-clincial evaluation of many nanoparticles for the delivery of theraupetic genetic materials. These will be screened developing and employing state-of-the-art biological evaluations adapted for nanoparticles. We plan to screen for thousands of formulation and aiming to identify few that will have a tremendous impact in both cancer therapy and motoneuron-degenerative disorders.

Planned Impact

In this proposal we aim to interface Chemistry and Bioengineering with Clinical Neuroscience and Oncology. This will allow the bridging of novel scientific discoveries into genuine medical applications through rigorous engineering characterisation. This is undoubtedly a very challenging and strategic project. If our ambitious objectives can be achieved, it would be very valuable in validating a novel biomedical delivery system for clinical studies with the potential to treat several neurological disorders. More importantly, we will benchmark the biological high-throughput evaluation of nanoparticles so as to accelerate future developments and hence assist translation from cutting-edge physical science to clinical applications. We intend to engage at an early stage with the Medicines and Healthcare products Regulatory Agency (MHRA) in order to facilitate this vision. MA and NB have extensive experience of taking new therapies through to the clinic. Any patentable work arising from this project will be protected and developed through the University's chosen commercialisation partner, Fusion IP. Furthermore, the existing strong collaboration with Biocompatibles is expected to facilitate eventual commercialisation. Appropriate contractual arrangements will be put in place to ensure that the technology can be exploited in a way that maximises its impact across the UK. The University has a network of specialist Corporate Industrial advisors and knowledge transfer specialists who can help in taking this technology through to market.
 
Description We have implemented a method to create nanoparticles based on block copolymers to be used for targeted delivery. The results have showed the creation of more complex and efficient systems that have been tested in both cancer targeting as well as targeting the blood system that control access to the central nervous system.
Exploitation Route We are now finalising our publications and we will also publish our protocols in our web pages to ensure maximum distribution. We hope that these methodologies will adopted by most group working in the nanomedicine field.
Sectors Chemicals,Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description The project was divided into two streams: one side we implemented new chemical method to create clinical compatible polymers. We have particularly builded on our previous finding to create alternative based on biodegradable and biocompatible materials. See Themistou, E., Battaglia, G., & Armes, S. P. (2014). Facile synthesis of thiol-functionalized amphiphilic polylactide-methacrylic diblock copolymers. Polymer Chemistry, 5(4), 1405-1417. and a further paper (using the same chemistry but for scaffold engineering) is under review with Biomacromolecules) Similar we have also optimised a new method to study surface topology on polymerise using metal labelling to identify polymer clusters with single chain resolution Manuscript under review with Polymer Chemistry Finally we established a group of protocols to perform nanomedicine discovery. These are performed in three stages, high content imaging using 2D cell culture assay based on cells associated with the targeted tissue (e.g. Brain endothelial cells for Blood brain barrier (BBB), or cancer cells for tumour targeting) whose uptake of nanoparticle is weighted against three sentinel cells (two immune cells and one stromal one). This high content screening is followed by a 3D in vitro assessment where we borrowed tools from tissue engineering to re-construct important physiological parameters. For the tumour models we constructed in vitro 3D solid tumour to asses tissue penetration and hence to identify nanoparticles capable of carrying therapeutic loads right to the core of the tumour. We joined our data with another ongoing project in the group and this paper was generated: Colley et al, Mol. Pharmaceutics, 2014, 11 (4), pp 1176-1188 For the BBB, we recreate a 3D polarised endothelial layer which contain CNS resident cells (e.g. Astrocytes) and perivascular cells (e.g. pericytes). This has allowed us to identify nanoparticles capable of actively trafficking across the tight blood barrier. Finally the successful formulations were tested in animal model with some very interesting outcome and validating our original hypothesis. The BBB work has been the most fruitful with one paper submitted in Scientific Report and currently under review Two more manuscripts are in preparation One to describe our in vitro 3D BBB model and one to detailed the high content screening protocol. The results are now being used to translate the technology to other clinical challenges including more focused Cancer targeting and several neurological disorders spanning from ALS, SMA, Parkinsons, Stroke and Alzehmeir. We have however set up a series of screening protocols that can be translated horizontally in several clinical applications as well as integrating them for drug discovery tools. We are now in negotiation with several pharmaceutical companies to perform some validation studies as well as discussing with UCLB the possibility to set up a spin out company
First Year Of Impact 2014
Sector 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 Delivery of antibody for therapeutic and diagnostic applications
Amount £56,768 (GBP)
Organisation BTG 
Department Biocompatibles
Sector Private
Country United Kingdom
Start 10/2011 
End 12/2014
 
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