Dynamic Drug Screening Platform
We provide a better analogue for the in vivo environment for permeability screening - all without having to change your current procedures!
Drug discovery is a long, costly, and high-risk process that takes over 10-15 years with an average cost of over $1-2 billion for each new drug to be approved for clinical use. There’s a growing need for highly accurate in silico and in vitro predictive models to facilitate drug discovery and development.
As oral delivery is the most convenient form of administration of pharmaceutical agents in terms of patience compliance, oral administration is preferred when possible. The absorption of orally administered drug products is a dynamic, complex process that depends on a number of biopharmaceutical properties, including a molecule's solubility, stability in the gastrointestinal tract (GIT), and permeability. In terms of regulation, the proportion of the oral dose that is absorbed is inextricably linked to the idea of high intestinal permeability.
Accurate assessment of a drug intestinal permeability is of critical importance during the drug development process, serving to guide both drug development and regulatory decisions. Results from in vitro permeation studies across the Caco-2 cell monolayer assay are commonly used for drug permeability screening in industry and are also accepted as a surrogate for human intestinal permeability measurements by the US FDA to support new drug applications. Poor intestinal permeability is viewed as an unfavourable biopharmaceutical property.
Problem: With current regulatory standards conveying the importance of compounds that have high intestinal permeability drug discovery and development programs that use Caco-2 as primary permeability screening tool may be disregarding viable drug candidates that are incorrectly predicted to be poorly permeable.
Discrepancies have only been observed for cases where some highly absorbed drugs have been predicted to be poorly permeable by Caco-2.Sstatic monolayer environment doesn't resemble the dynamic in vivo environment of the gut resulting in false-negative drug testing data.
Solution: MICA technology is a solution to that problem as we are able to easily add that necessary movement to the Caco-2 assay. Dynascreen is a bolt-on device to the standard Caco-2 assay. This is done by addition of MICA magnetic nanoparticles to the Caco-2 cell monolayer and its stimulation by a magnetic force.
MICA’s magnetic nanoparticles (MNPs) are targeted the Caco-2 cells' surface via specific coating. Thus, the mechanical forces required to create motility can then be applied remotely by a magnetic field acting on these magnetic particles. Whole process adds only 5 minutes to regular Caco-2 assay screening protocol and can be performed in MICA’s bioreactor which fits freely into standard lab incubator. Dynascreen is the first dynamic Caco-2 drug screening assay of its kind to better predict in vivo human drug absorption rates. Dynascreening outperforms standard assay by 150% apical to the basolateral direction and by 85% basolateral to apical direction in Paracetamol permeability screening.
Additionally it’s worth to mention that several countries have already developed strategic roadmaps to phase out animal experiments for regulatory purposes. This increases the need for a timely substitute that reflects physiology in the best possible manner. Dynascreen technology is a promising way forward in the preclinical and regulatory set up and will aid implementing 3R principle in basic science.
Dynamic drug absorption in Caco-2 cells can be up to 150% greater than static absorption assays;
Phase 4 compounds which showed limited absorption in static assays show absorption in our DYNASCREEN™ assays; and
DYNASCREEN™ is the first dynamic Caco-2 drug screening assay of its kind to better predict in vivo human drug absorption rates.
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