ABSTRACT

The intent of this chapter is to establish a comprehensive framework in which the physicochemical properties of permeant molecules, hydrodynamic factors, and mass transport barrier properties of the transcellular and paracellular routes comprising the cell monolayer and the microporous filter support are quantitatively and mechanistically interrelated. We specifically define and quantify the biophysical properties of the paracellular route with the aid of selective hydrophilic permeants that vary in molecular size and charge (neutral, cationic, anionic, and zwitterionic). Further, the quantitative interrelationships of pH, pKa, partition

coefficient, fractions of nondissociated and charged species, permeability coefficients of the aqueous boundary layer (ABL), filter support, and a cell monolayer with its component transcellular and paracellular routes are defined. The influence of stirring on the permeability coefficients of the ABL and cell monolayer are quantified. The aforementioned interrelationships are developed with data collected from models of permeability using cultured cells.