Basic Mechanisms in Transcellular and Paracellular Transport

Mammalian cell membranes separate cells from their environment and from one another. Cell membranes of the mucosal enterocyte linings consist of phospholipid bilayers in which proteins for signal transfer are incorporated.

Apical side

Apical side

Basolateral side

Figure 6.1. Transport routes across nasal respiration mucosa: (1) paracellular across tight junctions, (2) transcellular, and (3) transcytotic. Mucus secreting goblet cells (G), ciliated columnar cells (C), and tight junctions (Tj) are represented. Basal cells (B) are located on the basal lamina (Bl) adjacent to the lamina propria (Lp) with blood vessels. With permission from Junginger and Verhoef (1998)

Basolateral side

Figure 6.1. Transport routes across nasal respiration mucosa: (1) paracellular across tight junctions, (2) transcellular, and (3) transcytotic. Mucus secreting goblet cells (G), ciliated columnar cells (C), and tight junctions (Tj) are represented. Basal cells (B) are located on the basal lamina (Bl) adjacent to the lamina propria (Lp) with blood vessels. With permission from Junginger and Verhoef (1998)

These cell membranes are barriers to most polar compounds and also to macro-molecules, but they are relatively permeable to water and small hydrophobic molecules. Methods to facilitate transport of molecules, either small or large, across epithelial cells can be categorized into two major groups: transcellular and paracellular transport (Hayashi et al., 1997, Fasano, 1998) as highlighted in Fig. 6.1.

6.2.1 Transcellular Transport

As reviewed before, basic mechanisms of transepithelial transport of drugs include passive transport of small molecules, active transport of ionic and polar compound, and endocytosis and transcytosis of macromolecules (Fig. 6.1). Small and nonionic molecules usually cross cell monolayers by passive transport. The rate at which a molecule diffuses across the lipid bilayer of cell membranes depends largely on the size of the molecule and its relative lipid solubility. In general, the smaller and more lipophilic the molecule is, the more rapidly it will diffuse across the bilayer. However, cell membranes are also permeable to some small water-soluble molecules such as ions, sugars, and amino acids (Elsenhans et al., 1983.)

Passive transport is the movement of a solute along its concentration gradient. The passive transcellular transport of hydrophilic compounds, including macromolecules such as peptides, can be enhanced by interaction of the absorption-enhancing materials with both the phospholipid bilayer and the integrated proteins, thereby making the membrane more fluid and thus more permeable to both lipophilic and hydrophilic compounds.

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