Investigation of the adsorption of PEG1500-12-acyloxystearate surfactants onto phospholipid bilayers: an ellipsometry and cryo-TEM study

Abstract

In this article we present a study of a new class of surfactants denoted as PEG1500-12-acyloxystearates, which have potential use as pharmaceutical solubilizers. These amphiphilic molecules present interesting properties with regard to cell damage effects. PEG1500-12-acyloxystearates with C(14) to C(16) acyloxy chains cause little or no damage to red blood and intestinal cells, whereas the surfactants with shorter chains, from C(8) to C(12), induce measurable damage. To start unraveling the reason why there is this rather marked dependence of the cell damage effect on surfactant chain length, we have carried out systematic studies of adsorption properties of the surfactants onto phospholipid bilayers by means of ellipsometry. The rate of incorporation of the surfactants in the lipid membrane decreases with increasing length of the acyloxy chain. Cryo-TEM images strengthen the ellipsometry results by showing that the dissolution of the phospholipid bilayer is slower for the surfactants of the series having longer chains.

FIGURE 1

Structures of the PEG1500-12-acyloxystearate surfactants.

FIGURE 2

(A) Adsorbed amount of surfactant (circles) and adsorbed layer thickness (triangles) as a function of time for PEG1500C₁₈C₁₂ at phospholipid surfaces. The arrows refer to the moment when 0.5 μM of the surfactant solution was added into the cuvette and when the surface, after additional surfactant injections reaching a total concentration of 200 μM, was rinsed with buffer solution. (B) As in A, but for PEG1500C₁₈C₈. (C) As in A but for PEG1500C₁₈C₁₄.

FIGURE 3

Adsorbed amount of surfactant at phospholipid surfaces as a function of time for the different surfactants of the series studied: PEG1500C₁₈C₈ (solid circles), PEG1500C₁₈C₁₀ (triangles), PEG1500C₁₈C₁₂ (squares), PEG1500C₁₈C₁₄ (open circles), and PEG1500C₁₈C₁₆ (diamonds).

FIGURE 4

Adsorbed amount of surfactant as a function of time for all the different surfactants of the series studied on hydrophobized silica surfaces. Same symbols as in Fig. 3.

FIGURE 5

Cryo-TEM images obtained a half-hour after addition to DOPC liposomes of a PEG1500C₁₈C₈ micellar solution (A and B), PEG1500C₁₈C₁₂ (C and D), and PEG1500C₁₈C₁₆ (E and F).

FIGURE 6

Cryo-TEM images obtained 2 h after addition of a PEG1500C₁₈C₁₂ micellar solution to DOPC liposomes.

FIGURE 7

Cryo-TEM images obtained 24 h after addition of a PEG1500C₁₈C₁₆ micellar solution to DOPC liposomes.