MDCK Permeability

Solubility and permeability are important factors influencing drug absorption and are widely used to guide the development of new drugs. With extensive expertise in drug permeability and absorption and an experienced group of formulation experts, BOC Sciences offers MDCK Permeability service to accelerate early drug development.

Introduction

Drug permeability, which refers to the rate at which drug molecules pass through a given biofilm barrier, is one of the determinants affecting drug absorption through the intestine and oral bioavailability. Since oral administration is the preferred route of administration, successful therapy requires adequate intestinal absorption to ensure that the drug is available for its intended target. Good oral bioavailability occurs when the drug has maximum permeability and solubility at the site of absorption.

The degree of in vivo absorption can be predicted from solubility and permeability measurements. Experimental models of permeability in cell monolayers can assist in candidate selection during the early stages of drug discovery and development. The Madin-Darby canine kidney (MDCK) cell model is one of the commonly used cell monolayer systems for assessing the human intestinal barrier.

• Application of MDCK Permeability

The permeability coefficient measured by the MDCK model represents a fundamental relationship between the rate of drug absorption and the degree of absorption and can be used as a alternative method for predicting the absorption of orally administered drugs. Many of the physiological properties of MDCK cells are similar to the blood-brain barrier (BBB) and are also commonly used for in vitro drug crossing of the BBB Screening.

• Characteristics of MDCK Cells

MDCK cells share many of the same epithelial cell characteristics as Caco-2 cells, also have similar uptake and efflux transporters, and can form tight cell junctions in as little as 3 days. It was shown that the permeability data of passively absorbed drugs on the MDCK model and the Caco-2 model correlated well.

• Advantages of MDCK Permeability

In MDCK permeability testing, methods can be standardized based on pH conditions, transport direction, incubation time, drug concentration, and reference standards. The advantages of in vitro cell monolayer MDCK include passive diffusion, active transport and efflux across and by cells, the ability to perform mechanistic studies, the use of animal cell lines, and the ability to automate operations.

Our Methods

An MDCK permeability screen will be performed to detect the compound under test across the monolayer of MDCK cells.

Step 1: Cells are inoculated on a substrate (e.g., 24-well or 96-well plates) to form a monolayer of cells that morphologically and functionally resemble intestinal epithelial cells with barrier properties.

Step 2: The monolayer is placed in a diffusion apparatus containing apical (AP) and basolateral (BL) chambers, which represent the mucosal (lumen) and serosal (blood) surfaces of the intestine, respectively.

Step 3: The compound under test is added to the AP or BL chamber and its uptake or efflux is measured over time, respectively, to monitor the transport of the compound across the monolayer.

Step 4: Papp is measured as the rate of drug accumulation in the receiving chamber normalized against filtered area and chamber volume.

Why Choose BOC Sciences?

• Standardized parameters for assaying MDCK permeability
• Culture media composition
• Initial seeding density
• Feeding regimen
• Monolayer age
• Transport buffer composition and pH
• Transport temperature and time
• Co-solvent effects on cells
• Sink conditions and stirring process
• Sampling method
• Drug analysis and Papp calculation
• Measure of MDCK monolayer integrity
• In vitro permeability evaluation to accelerate early drug development
• Pursuit of high drug-forming properties for drug development
• Advanced MDCK permeability data collection and analysis techniques
• Good Laboratory Practice (GLP) compliant
• Proven preclinical drug permeability assays