Project: Development of a Drug-transporter Specific Ready-to-use Monolayer Cell Product Line: PReadyPort
AIM AND BUSINESS IDEA: _x000D_The business idea is to create stabilized and thus transportable ready-to-use drug transporter specific monolayer kits (PReadyPort) adaptable for automated platforms as well for on demand in vitro pharmacological barrier modelling and for single transporter interaction studies._x000D_SCIENTIFIC BACKGROUND:_x000D_(A) Role and importance of drug transporters:_x000D_The fate of administered compounds including drugs may largely depend on their interactions with drug transporter proteins, which are present in all major pharmacologically relevant barriers in the intestine, liver, kidney, brain, placenta, and testis. They modulate the pharmacokinetic properties of endobiotics and xenobiotics, among others by limiting or enhancing oral absorption, influencing the distribution of compounds. Similarly, drug-transporter interactions may modulate the bioavailability of other compounds, e.g. reduce their excretion rate, or when co-administered with another drug may influence the efficacy of the drug(s). Thus, transporters may also be the site of drug-drug, drug-nutrient and drug-endobiotic interactions and therefore be responsible for many adverse drug reactions. _x000D_(B) The importance of MDCKII monolayer assays:_x000D_Monolayer systems consist of a tight cell layer grown on a porous support that separates two fluid compartments. They are widely regarded as the most sophisticated state of the art in vitro tools for medium to high throughput modeling of important pharmacokinetic barriers such as intestinal epithelium, blood-brain-barrier etc. Monolayers have become an industry standard for the investigation of intestinal absorption. Development of specific transporter transfected MDCKII cell lines that form tight cell layers brought about the possibility of investigating single transporter interactions on monolayers, while the introduction of double transfected cell lines, where an apical efflux transporter is located opposite a basolateral uptake transporter with overlapping substrate specificities, allowed the efficient vectorial transport of substrates and thereby experiments on low passive permeability molecules. _x000D_GENERAL DESCRIPTION OF THE PROJECT CONSORTIUM:_x000D_The consortium is formed by renowned experts of ADME-Tox commercial applications. Solvo Biotechnology has now 10 years of experience with ABC transporters. Solvo is the leading provider of transporter technology, assays and reagents and became a recognised brand in its field worldwide. Solvo is a highly innovative company in developing reagents, cell lines, cell-based systems, chemicals, drug targets, test kits and turn key solutions as a CRO. Solvo is unique among its competitors that it provides with its products references based on its own research published in peer reviewed scientific journals. Solvo is actively participating in international research networks. The Sixth Framework Programme provided the applicants to work together in the LIINTOP project (Optimisation of liver and intestine in vitro model for pharmacokinetics, and pharmacodynamics studies, LSHB-CT- 2006-037499). In this project, applicants Solvo and Advancell taking part in the implementation of “Transport & Metabolism Testing Methods” work package while Advancell is involved in three other work packages in Liintop._x000D_Advancell has 8 years of experience in biotechnology with primary competencies in the development of cell-based in vitro models for the testing mechanism of action of drug canditates, nanomedicine using natural polymer Nanosystems to improve the administration of drugs and modulate their bioavailability and drug developments. Advancell is working close together with the local universities and hospitals and has extensive experience in commercializing ready-to-use cell-based kits since 2005 all over Europe, and US since January 2009. Advancell is the innovator of the proprietary shipping medium that allows safe transport of preplated living cells. _x000D_We wish to capitalise on the diverse and complementary skills of Solvo and Advancell to develop this new product line. The proposed project stems from the unique expertise of Solvo in the development of in vitro drug transporter assays, and on the expertise of Advancell in living cell shipping technology and on their special patented conditioning medium, which makes the system very user-friendly for handling requirements._x000D_Solvo and Advancell aim to be the first and exclusive innovators on the market and leaders in the field of the PReadyPort products while meeting an unmet need: A transportable, roboust, ready to use, off the shelf in-vitro assaying system that is able to detect and reveal transporter mediated drug interactions. We believe that the envisaged PreadyPort system will be able to address this specific market need._x000D_The Ps have been selected upon excellence in research backgrounds, resources, facilities, and on their expertise and reputation on the targeted market.
| Acronym | PReadyPort (Reference Number: 5330) |
| Duration | 01/11/2009 - 28/02/2012 |
| Project Topic | The aim of the project is to develop and commercialize cell-based transportable ready-to-use drug transporter specific monolayer kits (PReadyPort) for in vitro pharmacological barrier modelling for transporter interaction studies for pharmaceutical, biotech, cosmetic, and consumer goods industries. |
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Project Results (after finalisation) |
This project aimed the development and market introduction of products, based on living, transfected cells, that aim the better prediction of the interaction of drug like molecules with drug transporter proteins._x000D__x000D_The novelty in this approach is to enable these kind of studies at locations where cell culturing facilities or expertise is limited. Since these in vitro experiments solely rely on cells, the potential market reach is significantly elevated as compared to providing services or sublicensing the cell lines themselves._x000D__x000D_The project was a collaborative effort between Solvo Biotechnology and initially Advancell SA, then later Leitat when Leitat bought in vitro testing department of Advancell._x000D__x000D_In this project we focused on products based around the two major drug efflux transporters P-glycoprotein (MDR1, ABCB1) and Breast Cancer Resistance Protein (ABCG2). We developed and validated kits based around cells producing these proteins in 24 well as well as 96 well platforms._x000D__x000D_We also developed products based on double transfectants expressing two transporters on opposite membrane doCOs of the cell, mimicking transport events across pharmacological barrier tissues. The NTCP (SLC10A0)-BSEP(ABCB11) double transfectant mimics flow of bile constituents across the hepatocyte. However after lengthy unsuccessful molecular biology work we abandoned the cell line in favor of a kidney transport model OAT1(SLC22A6)-BCRP. We managed to develop and validate the cell line and move into validation phase of the product._x000D__x000D_The OATP-B (SLCO2B1)-BCRP is model of material flow across hepatocytes. Within the project timeframe we validated the cell line and validated the kits based on it. |
| Network | Eurostars |
| Call | Eurostars Cut-Off 3 |
Project partner
| Number | Name | Role | Country |
|---|---|---|---|
| 2 | ADVANCELL ADVANCED IN VITRO CELL TECHNOLOGIES, S.A. | Partner | Spain |
| 2 | SOLVO Biotechnology | Coordinator | Hungary |