Permeability transport mechanisms

Transport. Wood is composed of a complex capillary network through which transport occurs by capillarity, pressure permeability, and diffusion. A detailed study of the effect of capillary stmcture on the three transport mechanisms is given in Stamm (13). 

A different approach is the use of an ultrafiltration membrane with an immobilized chiral component [31]. The transport mechanism for the separation of d,l-phenylalanine by an enantioselective ultrafiltration membrane is shown schematically in Fig. 5-4a. Depending on the trans-membrane pressure, selectivities were found to be between 1.25 and 4.1, at permeabilities between 10 and 10 m s respectively (Fig. 5-4b). 

The enthusiasm for using Caco-2 cells and other epithelial cell cultures in studies of drug transport processes has been explained by the ease with which new information can be derived from these fairly simple in vitro models [7]. For instance, drug transport studies in Caco-2 cells grown on permeable supports are easy to perform under controlled conditions. This makes it possible to extract information about specific transport processes that would be difficult to obtain in more complex models such as those based on whole tissues from experimental animals. Much of our knowledge about active and passive transport mechanisms in epithelia has therefore been obtained from Caco-2 cells and other epithelial cell cultures [10-15]. This has been possible since Caco-2 cells are unusually well differentiated. In many respects they are therefore functionally similar to the human small intestinal enterocyte, despite the fact that they originate from a human colorectal carcinoma [16, 17]. 

Fig. 7.1. The intestinal permeability of drugs in vivo is the total transport parameter that may be affected by several parallel transport mechanisms in both absorptive and secretory directions. Some of the most important transport proteins that may be involved in the intestinal transport of drugs and their metabolites across intestinal epithelial membrane barriers in humans are displayed.

Fagerholm, U., Lindahl, A., Lennernas, H., Regional intestinal permeability in rats of compounds with different physicochemical properties and transport mechanisms, /. Pharm. Pharmacol. 1997, 49, 687-690. 

Evans, D. H. (1984). The roles of gill permeability and transport mechanisms in euryhalinity. In Fish Physiology, Vol. XB, Gills, Ion and Water Transport, eds. Hoar, W. S. and Randall, D. J., Academic Press, London, pp. 239-284. 

Fagerholm U, Lindahl A and Lennernas H (1996b) Regional Intestinal Permeability for Compounds with Different Physico-Chemical Properties and Transport Mechanisms in Rats. Eur J Pharm Sci 4 pp 153. 

Kurosaki Y, Yano K, Kimura T (1998) Perfusion cells for studying regional variation in oral mucosal permeability in humans. 2. A specialized transport mechanism in D-glucose absorption exists in dorsum of tongue. J Pharm Sci 87 613-615... 

The following sections provide an overview of the application of the IPL for the study of drug absorption. Examples are provided to illustrate the use of the IPL to study drug permeability, absorption profiles, transport mechanisms and the effects of inhaled dose formulation on drug disposition. 

Caco-2 cells have been valuable in the estimation of drug absorption potential, transport mechanisms, and effect of permeation enhancers on transepithelial transport.35,39,53,67-69,78-81 Owing to the sensitivity of the cells and the limited solubility of new molecular entities, Caco-2 permeability studies are routinely done with relatively low concentration of compounds. One way to increase the solubility of these compounds is to use organic solvents. The low tolerability of Caco-2 cells to organic solvents limits the use of this approach in permeability studies. 

---