Drug Transport across Xenopus Alveolar Epithelium in Vitro

Abstract

Biopharmaceutical polypeptides are usually relatively large, hydrophilic molecules with considerable susceptibility to hydrolase degradation and very low epithelial permeability. These features result in poor oral and transdermal absorption and limit most compounds presently on the market to injectable formulations. Recently, data illustrating relatively high bioavailability for polypeptides administered via the pulmonary route (Adjei and Gupta, 1994; Patton et al., 1993; Wall, 1995) and the feasibility of generating small-particle aerosols of some of these molecules (Niven, 1993; Cipolla et al., 1994) have increased interest in mechanisms of macromolecular transport across the lung epithelium. Although many polypeptides have much higher bioavailability in animals when administered by the pulmonary than by the oral route, this does not apply to all compounds, particularly those susceptible to proteolytic cleavage (Adjei and Gupta, 1994; Patton et al., 1993; Wall, 1995). In addition, the time course of absorption across the lung is quite variable, with some small molecules (e. g., the cationic antibiotic pentamidine) having very little absorption compared to much larger compounds (Montgomery et al., 1988). Systematic evaluation of the factors determining rate and extent of transport across pulmonary epithelium is needed to understand and predict when pulmonary delivery may be a successful approach to consider for drug molecules.