Interactions between Amphotericin B and Sterols in Monolayers. Mixed Films of Amphotericin B-Cholesterol

Abstract

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.

Mixed Monolayers of Cyclosporin-A and Phospholipids at the Air–Water Interface

“…2, the π -A curves corresponding to mixed monolayers of DPPC containing variable fractions of CsA shift along the X -axis; thus, the addition of the phospholipid to the pure CsA monolayer causes it to condense at a surface pressure below 30 mN/m and to expand above that level. A similar effect has been observed in all the mixtures studied and by other authors in mixed systems of various components (11,12).…”

“…[12] Once the mixing process has been completed the mixed monolayer is compressed until the initial superficial tension γ is reached. The variation in free energy corresponding to this third process is…”

Interactions between membrane sterols and phospholipids in model mammalian and fungi cellular membranes — A Langmuir monolayer study

“…To understand their role in the polyenes mechanism of action, it is of utmost importance to study the interactions between the antibiotic and phospholipids in the presence of sterols. Until now, the Langmuir monolayer technique was applied to examine the interactions between polyene antibiotics and either sterol [20,21] or phospholipids [22,23]. However, to understand the complex mechanism of action of the polyene antifungal it is necessary to study the interactions between the antibiotic and the lipidic components of the fungi and mammalian cellular membranes (phospholipids and sterols).…”

Desorption of Amphotericin B from Mixed Monolayers with Cholesterol at the Air/Water Interface

“…The characteristics of mixed AmB/cholesterol monolayers have already been reported; however, the experimental conditions applied therein were different than those in the present work. Nevertheless, the overall behavior is similar and for a detailed analysis of the mixed Langmuir isotherms the readers are referred to our previous papers (4,6). The relaxation experiments carried out for the AmB monolayer alone (9) confirm that amphotericin molecules undergo desorption from the surface.…”

“…It is believed that AmB acts through linking to membrane sterols (2) to make complexes responsible for the formation of internal channels (3) by which crucial elements escape from the cell, causing its damage and eventually death. To get further insight into AmB's mechanism of action, we have been researching the surface behavior of AmB alone as well as its interaction with sterols in monolayers at the air/water interface (4)(5)(6). The pressure/area (π/A) isotherm of AmB exhibits a characteristic transition plateau which separates two regions of liquid-expanded and liquid-condensed states (7,8).…”