Mixtures of cholesterol with stearic (STA), oleic (OA), and linoleic (LA) acids spread as monolayers at the air/water interface were used as model systems to examine the hypocholesterolemic effect of fatty acids. Miscibility and interactions between the components of the cholesterol/fatty acid systems were studied basing on the analysis of surface pressure/area isotherms completed with Brewster angle microscopy images. In monolayers, STA and cholesterol were found to be immiscible. In contrast, OA and LA were found to form miscible, but nonideal mixed monolayers with cholesterol. They exhibit negative deviations from ideality in the surface pressure/area plots. This reflects close-packing arrangements between bulky cholesterol molecule and the hydrocarbon chains of unsaturated fatty acids. The analysis of the excess free energies of mixing shows that the maximum negative value of ΔG exc appears at about X chol = 0.5−0.7. Thus, the formation of the most stable 1:1 and 2:1 complexes between cholesterol and an unsaturated fatty acid molecule may account for the hypocholesterolemic effect of the acids in human organism by complexing free cholesterol, thereby hindering its deposition on artery walls.

π−A isotherms of mixed monolayers composed of cholesterol and amphotericin B (AmB) spread on aqueous buffers of various pH and temperatures show the existence of interactions between the two components, which are more pronounced when the mole fraction of AmB is 0.7. As a consequence of the interactions, the excess areas and excess free energies of mixing are negative at low surface pressures and positive at high surface pressures. These results suggest that negative deviations of the additivity rule are due to the formation of a hydrogen-bonded AmB−cholesterol complex in which AmB molecules are oriented horizontally at the interface and cholesterol molecules lie vertically. The positive excess areas of mixing at high surface pressures could be due to AmB being less desorbed in the substrate by composition-dependent van der Waals interactions between the apolar moieties of the components, both oriented in this situation in a vertical position at the A/W interface.

Using the monolayer technique to study the surface behaviour of systems consisting of amphotericin B (AmB) and various sterols, the components were found to interact with each other. The interactions observed are accounted for by postulating that, at low surface pressures, AmB and different sterols form mixed films where the former lies parallel and the latter normal to the air-water interface in such a way that the polar groups in both components establish hydrogen bonds that lead to the formation of an AmB-sterol 'complex' of 2:1 stoichiometry at the interface. At high surface pressures, AmB molecules rearrange themselves normal to the interface; this gives rise to the Van der Waals interactions between non-polar chains of both components that vary with the nature and composition of the system. The occurrence of these hydrophobic interactions prevents the desorption of AmB into the subphase, which is consistent with the positive excess areas of mixing obtained under these surface pressure conditions. Among the four sterols studied, ergosterol exhibits the strongest interaction with AmB and beta-sitosterol the weakest. Cholesterol and stigmasterol show intermediate behaviour.

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