The Case For The Ideal In Vitro Artificial Membrane Permeability Model

7.4.1 Lipid Compositions in Biological Membranes

Different tissues have different lipid compositions. The most common lipid components of membranes are PC and PE. Lipid extracts from brain and lung are also rich in PS; heart tissue is rich in PG, and liver is rich in PI [567]. Human blood cells, as ''ghost'' erythrocytes (with cytoplasm contents removed), are often used as membrane models. These have different compositions between the inner and outer leaflets of the bilayer membrane. Phospholipids account for 46% of the outer leaflet membrane constituents, with PC and Sph about equal in amount. The inner leaflet is richer in phospholipids (55%), with the mix: 19% PE, 12% PS, 7% PC and 5% Sph [567].

Proulx [571] reviewed the published lipid compositions of brush-border membranes (BBM) isolated from epithelial cells from pig, rabbit, mouse, and rat small intestines. Table 7.1 shows the lipid makeup for the rat, averaged from five reported studies [571]. Kramer et al. [572,573] reported Madin-Darby canine kidney (MDCK) and BBB lipid composition profiles, listed in Table 7.1, for comparative purposes. Also shown are typical compositions of soy- and egg-derived lecithin extracts. Sugano's composition [561,562] is an attempt to mimic the BBLM. Table 7.1 lists the anionic-to-zwitterionic lipid weight ratios. On a molar basis, cholesterol accounts for about 50% of the total lipid content (37% on a weight basis) in the BBLM. The cholesterol content in BBLM is higher than that found in kidney epithelial (MDCK) and cultured brain endothelial cells (Table 7.1). (Slightly different BBLM lipid composition was reported by Alcorn et al. [433].) The outer (luminal) leaflet of the BBLM is rich in sphingomyelin, while the inner leaflet (cytosol) is rich in PE and PC. Apical (brush border) and basolateral lipids are different in the epithelium. The basolateral membrane content (not reported by Proulx) is high in PC, whereas the BBM has nearly the same PC as PE content. It appears that the BBB has the highest negative lipid content, and the BBM has the lowest negative lipid content of the three systems listed in the table. Cholesterol content follows the opposite pattern.

7.4.2 Permeability-pH Considerations

The effective permeability of ionizable molecules depends on pH, and the shapes of the permeability-pH profiles can be theoretically predicted when the pKa of the molecule is known, the pH partition hypothesis are valid, and the resistance of

TABLE 7.1 Lipid Compsitions (%w/w) of Biological Membranes"
0 0

Post a comment