Technologies for the Treatment of Brain Diseases
Lead Research Organisation:
UNIVERSITY OF EXETER
Department Name: Physics
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
People |
ORCID iD |
Julian Moger (Principal Investigator) |
Publications
Lalatsa A
(2012)
Delivery of peptides to the blood and brain after oral uptake of quaternary ammonium palmitoyl glycol chitosan nanoparticles.
in Molecular pharmaceutics
Garrett N
(2012)
Exploring uptake mechanisms of oral nanomedicines using multimodal nonlinear optical microscopy
in Journal of Biophotonics
Garrett N
(2012)
Label-free imaging of polymeric nanomedicines using coherent anti-stokes Raman scattering microscopy
in Journal of Raman Spectroscopy
Moger J
(2012)
Imaging cortical vasculature with stimulated Raman scattering and two-photon photothermal lensing microscopy
in Journal of Raman Spectroscopy
Mazza M
(2013)
Nanofiber-based delivery of therapeutic peptides to the brain.
in ACS nano
Goodhead RM
(2015)
Tracing engineered nanomaterials in biological tissues using coherent anti-Stokes Raman scattering (CARS) microscopy - A critical review.
in Nanotoxicology
Description | The poor bioavailability of peptides, nature's own 'drugs', limits their therapeutic application. Molecular envelope technology (MET) delivery allows their use as nanoenabled medicines, with an up to 18-fold increase in brain levels. The multi-disciplinary 'Peptide Pill' consortium aimed to develop the pain peptide pill METDoloron. 20% of European adults suffer from chronic pain often inadequately controlled by opioids, which often have life threatening side effects. METDoloron avoids these problems by targeting a different receptor and using an endogenous peptide and is therefore expected to have a significant impact on the large (US$ 50 bn), fragmented, and growing pain market for pain. This project was part of a larger consortium lead by The London School of Pharmacy (UCL), to confirm the pharmacology, transport mechanisms, established scale-up and manufacturing processes, and confirm product safety of METDoloron. In achieving this the project created new know-how in biophotonics, pain therapy, flow reactor design and nanoparticle processing techniques. Exeter's specific contribution to the project was to provide novel information on mechanisms by which the nanoparticles enhance the delivery of the drugs from both oral and IV routes to the brain. Exeter have leading expertise in the application of non-linear optical microscopy for imaging the interaction of nanomaterials in biological tissues and in a long-standing collaboration with the London School of Pharmacy have developed label-free optical imaging techniques to provide mechanistic data regarding the uptake of polymeric nanomedicines. The label-free nature of these developmental techniques proved essential since they remove the reliance on fluorescent markers which are know to perturb the transport kinetics of drugs. This project made the following key contributions to the development of METDoloron: 1. Using Coherent Raman Scattering (CRS) microscopy we detected deuterated polymeric nanoparticles within mice and rats following a range of dosing routes. We have confirmed that after oral dosing in mice, the particles cross the epithelium of the intestine, from whence they travel to the liver, kidneys and lungs. We have identified several cell types (hepatocytes, white blood cells etc.) inside which the particles are found in discrete volumes of 1 - 6 microns, co-localised with strong CH signal, which suggest potential clearing mechanisms of the particles from the body. The discovery of particles within the liver hepatocytes and bile canaliculi provides further evidence for the recirculation pathway of these particles from the Gi tract to the liver and then back into the gut via the release of bile from the gall bladder. 2. We have demonstrated the adherence of particles to the endothelium of blood vessels within the brains of mice after IV dosing. However, there was no evidence for adherence of these particles to peripheral vasculature, which suggests that the particles preferentially adhere to blood vessels within the brain. 3. Nasal dosing of rats has also shown to be an effective technique for transferring particles into the brain. We have shown that the particles are found in the olfactory bulb at 2 and 5 minutes after nasal dosing, and within the basal ganglia at 1 hour after nasal dosing. |
Exploitation Route | To fully exploit the potential impacts of METDoloron, Nanomerics has entered into a mutually beneficial alliance with Depomed in order to progress METDoloron to clinical development (please see accompanying GANNT chart). Depomed has product launch experience, having recently launched a neuropathic pain product - Gralise, and have a marketing resource and a contracted sales force. To fully exploit the MET platform and generate partnering opportunities, Nanomerics will aggressively market its capability once each of the key validation steps has been reached, e.g. on achieving dosage form scale up, on filing an investigational new drug application and particularly once METDoloron has been validated in humans. The main output from this research is a set of protocols, data and materials that will lead to the first in human trials of molecular envelope technology for the delivery of peptides (MET Doloron). The launch of METDoloron, a new pain therapeutic with a better safety profile, should contribute to the UK's economic competitiveness, as royalties will flow to Nanomerics. With respect to quality of life improvements METDoloron is expected to provide improved pain therapy, with fewer deleterious side effects for some of the 80% of the world's population that have inadequate access to pain relief. The project also has indirect effects on UK R&D because of its strategic importance for the partnering companies. The project brought together the capabilities of two innovative technologies, Nanomerics' MET platform technology and AMT's Coflore system. Both enabling technologies with clear USPs and product profiles that make them attractive for their target markets. Nevertheless, significant market entry barriers existed for both novel technologies, in particular in the pharmaceutical industry. This project demonstrated the effectiveness of both technologies for this industry thus dramatically reducing market barriers and allowing the partner companies to attract further UK R&D investment for additional projects. |
Sectors | Chemicals,Healthcare,Pharmaceuticals and Medical Biotechnology |
Description | Findings from this award have been used to leaver funding to develop a novel nano medicine that will be taken to clinical trials. |
First Year Of Impact | 2015 |
Sector | Pharmaceuticals and Medical Biotechnology |
Impact Types | Economic |
Description | University of Exeter |
Amount | £95,034 (GBP) |
Funding ID | TS/J004820/1 |
Organisation | University of Exeter |
Sector | Academic/University |
Country | United Kingdom |
Start | 08/2012 |
End | 08/2014 |