Concentrated and Charged Phospholipid Membranes

Hydrogen bonding and electrostatic interactions between the sample molecules and the phospholipid bilayer membranes are thought to play a key role in the transport of such molecules. When dilute 2% wt/vol phospholipid in alkane is used in the artificial membrane [15, 23], the effect of hydrogen bonding and electrostatic effects may be underestimated. 

Recently in our group, model membrane permeation barriers have been constructed with concentrated phospholipid solutions, 10-74% wt/vol soy lecithin (approximate %w/w lipid composition 24% PC, 18% PE, 12% PI cf. Table 3.1) in dodecane, supported on high-porosity, hydrophobic microfilters. This newly formulated lipid has a net negative charge at pH 7.4, which further increases above pH 8, as the ethanolamine groups deionize. Also tested were 10% wt/vol egg lecithin lipid solutions in dodecane (approximate composition 73% PC, 11% PE, 

2% LysoPI). The inositol content was four times higher in soy than in egg lecithin. 

However, when up to 74% phospholipid fractions are used, severe experimental problems arise. With lipophilic sample molecules, the use of concentrated phospholipid artificial membranes leads to two unwanted effects (1) near-complete membrane retention (90-100%) and (2) highly diminished permeability (extinguished in some cases). Both of these effects are presumably due to excessive drug-membrane binding. 

These adverse effects are almost eliminated by using an ionic surfactant to create a very strong sink condition in the acceptor compartment of the permeation cell, and this is the principal focus of our latest research. The charge on the micelles formed from the surfactant also appears to play a role in this respect. 

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