Development and validation of a dynamic drug screening platform for ADME testing
Lead Research Organisation:
Keele University
Department Name: Inst for Science and Tech in Medicine
Abstract
The Caco-2 cell line is the gold standard for the prediction of drug absorption and permeability in vitro by mimicking the
small intestine. However, this model lacks the dynamic motion which represents one of the physiological functions of the
small intestine (peristalsis). In our research, we investigate the possible similarity between the static Caco-2 cell model and
the dynamic intestine by creating a dynamic in vitro environment using MICA technology. In order to obtain the dynamic
cells environment, MICA Biosystems' technology was applied to the Caco-2 cell line. With this technology it is possible to
interact, by the application of an external magnetic field, with the magnetic core nanoparticles specifically attached on the
cells membrane, and produce deformations on the membrane which mimic a dynamic cell in vivo environment e.g. in the
case of the gut similar to peristaltic contractions. Our results to date have shown that MICA' technology improves the
absorption of the selected drugs, and their permeability is more similar to that found in the human intestine. Our data
suggests that MICA' technology applied to Caco-2 drug permeability assay could be used to better predict, using in vitro
assays, the in vivo human drug absorption rates. This feasibility study will enable us to test rigorously against the gold
standards and generate a new assay for the pharmaceutical market.
small intestine. However, this model lacks the dynamic motion which represents one of the physiological functions of the
small intestine (peristalsis). In our research, we investigate the possible similarity between the static Caco-2 cell model and
the dynamic intestine by creating a dynamic in vitro environment using MICA technology. In order to obtain the dynamic
cells environment, MICA Biosystems' technology was applied to the Caco-2 cell line. With this technology it is possible to
interact, by the application of an external magnetic field, with the magnetic core nanoparticles specifically attached on the
cells membrane, and produce deformations on the membrane which mimic a dynamic cell in vivo environment e.g. in the
case of the gut similar to peristaltic contractions. Our results to date have shown that MICA' technology improves the
absorption of the selected drugs, and their permeability is more similar to that found in the human intestine. Our data
suggests that MICA' technology applied to Caco-2 drug permeability assay could be used to better predict, using in vitro
assays, the in vivo human drug absorption rates. This feasibility study will enable us to test rigorously against the gold
standards and generate a new assay for the pharmaceutical market.
Planned Impact
The project will advance scientific output and generate new knowledge over multiple research areas. These developments
will advance global research in magnetic nanotechnology and biotechnology with potential for significant and wide ranging
academic impact. Further to this the project will build cross-linking expertise by bringing together academics with workers in
the industrial biomedical sector. It will thus provide a training forum to deliver highly skilled researchers with cross
disciplinary expertise in nanotechnology and biomedical areas. Through this, the proposal will also deliver cultural impact
by providing part of the landscape of a highly educated workforce. The project will have strong impact in the
business/industrial sector where nanoscale technology impact in the Life Science market is predicted to rise from $145M in
2007 to $5670 in 2015 (Nanomaterials and Markets 2008-2015, Nanoposts, 2008). The proposed research would leave the
UK ideally positioned to exploit growth in this sector by promoting major advances in bio/nanotechnology competences,
and leading innovation through the translation of these strengths into the Life Science sector.
A significant impact will be improved healthcare and better worldwide life quality, providing global benefits to society.
Further, economic and societal impact will be generated by enhancing quality of life and health, and by enhancing the
effectiveness of public services. Additional benefits for the general public will emerge from the generation of new bionanotechnology
commercial areas and enhanced competitiveness (in research, innovation and education), creating
employment opportunities in the UK and elsewhere (e. g., by creating spin-out companies and new commercial enterprise
partnerships) and making the UK more attractive to researchers and other professionals from the rest of the world.
will advance global research in magnetic nanotechnology and biotechnology with potential for significant and wide ranging
academic impact. Further to this the project will build cross-linking expertise by bringing together academics with workers in
the industrial biomedical sector. It will thus provide a training forum to deliver highly skilled researchers with cross
disciplinary expertise in nanotechnology and biomedical areas. Through this, the proposal will also deliver cultural impact
by providing part of the landscape of a highly educated workforce. The project will have strong impact in the
business/industrial sector where nanoscale technology impact in the Life Science market is predicted to rise from $145M in
2007 to $5670 in 2015 (Nanomaterials and Markets 2008-2015, Nanoposts, 2008). The proposed research would leave the
UK ideally positioned to exploit growth in this sector by promoting major advances in bio/nanotechnology competences,
and leading innovation through the translation of these strengths into the Life Science sector.
A significant impact will be improved healthcare and better worldwide life quality, providing global benefits to society.
Further, economic and societal impact will be generated by enhancing quality of life and health, and by enhancing the
effectiveness of public services. Additional benefits for the general public will emerge from the generation of new bionanotechnology
commercial areas and enhanced competitiveness (in research, innovation and education), creating
employment opportunities in the UK and elsewhere (e. g., by creating spin-out companies and new commercial enterprise
partnerships) and making the UK more attractive to researchers and other professionals from the rest of the world.
| Description | This project was concerned with the development of a dynamic assay to provide an in vitro model that better predicts human intestinal permeability, and to evaluate this as a method to screen different drug compounds. In order to do this we successfully developed protocols for preparing and characterising magnetic particles with coatings optimised for binding to cell monolayers. The cell monolayers were then mechano-stimulated using a commercial magnetic bioreactor and the permeability of the different compounds was assessed. It was found that, for a range of drug compounds, the permeability measured by the dynamic system was closer to reference in vivo measurements than a comparable static method, thus validating the approach applied. |
| Exploitation Route | There is potential for commercial development of the work. Our results to date as part of an Innovate funded Feasibility study have shown that MICA technology improves the absorption of the selected drugs, and their permeability is more similar to that found in the human intestine. We are now at the stage of validation of our assay with a partner ADME contract research organisation (CRO) before potential commercialisation of the product. We recently obtained further InnovateUK/TSB funding for a short term (6 month) project that will enable us to create the final QA steps and the validation of the assay in an ADME CRO environment using validated drug compounds. The final stages will include creation of standard operating procedures (SOPs) alligned to the existing assay and design of new QA steps for the protocol. |
| Sectors | Chemicals,Healthcare,Pharmaceuticals and Medical Biotechnology |
| Description | The methods developed in the project are currently being evaluated by our industrial partner. |
| First Year Of Impact | 2015 |
| Sector | Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
| Impact Types | Economic |
| Description | Technology Strategy Board - CR&D PROPOSAL (Open call for all competitions) |
| Amount | £19,511 (GBP) |
| Funding ID | TS/P006353/1 |
| Organisation | Innovate UK |
| Sector | Public |
| Country | United Kingdom |
| Start | 04/2017 |
| End | 09/2017 |