Predict Your Test Compound Suitability for Oral Dosing with Caco-2 Permeability Assay

Caco-2 cells are highly useful for intestinal absorption studies due to their ability to model human absorption characteristics. The Caco-2 assay is widely utilized in drug discovery for assessment of compound permeability properties. 

Using the caco-2 cell line to assess compound permeability you will be able to differentiate compounds which are likely to pose challenges during preclinical and clinical development. Test compounds with poor permeability are more likely to have poor Absorption, Distribution, Metabolism, Excretion (ADME) and Pharmacokinetics (PK) properties.

When Caco-2 cells are cultured as a monolayer, this human colon carcinoma cell line forms characteristics that mimic intestinal epithelial cells, such as the formation of a polarized monolayer with an apical brush border, which forms tight junctions. This apical brush border contains many of the enzymes and transport proteins that mediate the active uptake or efflux of drugs and chemicals in the intestine.

By assessing the transport rate of a compound across a Caco-2 cell monolayer membrane, the in vivo absorption of the compound across the gut wall can be predicted.

Key Points about Caco-2 Permeability Assay are:

• The Caco-2 permeability is an FDA recommended assay for organizations applying for an Investigational New Drug (IND). It is utilized as a model of human intestinal absorption of drugs.
• When run with a reliable CRO, the Caco-2 permeability assay can assess suitability of your test compound for oral dosing.
• Additional evaluations can be made, including whether a test compound is actively transported by P-glycoprotein (P-gp).

Choosing a Professional Contract Research Organization (CRO) to Run a Caco-2 Study

When looking to run a Caco-2 permeability study, check whether the organization follows GCCP and GIVIMP guidelines. This is a good indicator of experience with in vitro methods and what the quality of the data will be.

IONTOX, L.L.C. is a CRO specializing in vitro methods. IONTOX ‘s Caco-2 permeability assay is overseen by a Diplomat of the American Board of Toxicology and follows the internationally recognized guidance documents on Good In Vitro Method Practices (GIVMP) and Good Cell Culture Practices (GCCP).

For more information regarding Caco-2 permeability assay, visit https://www.iontox.com/caco-2-permeability-assay/ today.

Choose Physiologically Correct Microphysiological System

Although, great strides have been made in-regards to in vitro and in vivo research, limitations have been realized around the physiological and genetic relevance of traditional in vitro and animal models.

To address this challenge, microphysiological systems (MPS) have been developed as a solution to the present limitations of current in vitro and in vivo research through the use of integrated organ models in combination with advanced cell and tissue models. The ultimate goal for these microphysiological systems is to give researchers a system with enough physiological relevance to create PBPK models that can be utilized to predict systemic toxicity in humans, in vitro.

The ideal microphysiological systems should have the following features:

• A simulated blood flow with separate fluid compartments, which allow each organ compartment to be cultured in the cell or tissue’s optimal growth media.
• A design that allows for various advanced cell lines and tissue types from trusted suppliers to be used.
• Cell and tissue wells made of plastics compatible with cell and tissue culture.
• A design at a scale that allows researchers to collect biochemical and molecular absorption data essential for understanding drug-organ interactions and the ADMET of a compound.
• A system and data shown to be physiologically relevant enough to create PBPK models capable of predicting toxicity in humans.

The Human Dynamic Multiple Organ Plate (HuDMOP™) from IONTOX was designed with these key experimental needs of a microphysiological system in mind. In the HuDMOP™ system, organs are represented by 2D or 3D models and connected to one another via a simulated blood flow system. This patented simulated blood flow system allows for communication between organ compartments without a complete exchange of culture media by utilizing a semipermeable membrane. This semipermeable membrane, along with the simulate blood flow, increases the physiological relevance of the system and allows each cell or tissue type to be cultured in their optimal growth media.

In addition to the simulated blood flow, the HuDMOP™system allows organizations the option to use various advanced 3D cell and tissue models with plastics that are designed for cell culture.

Finally, HuDMOP™’s larger meso-scale size allows organizations seeking a microphysiological system the ability to collect the necessary biochemical and molecular absorption data through HuDMOP™for an understanding of drug-organ interactions and the ADMET of a compound. With the key aspects discussed above in mind, the HuDMOP™ system has been shown in preliminary studies to be physiologically relevant enough to build PBPK models capable of predicting toxicity in humans.

For more information on HuDMOP™ visit iontox.com today.