Influence of a Spreading Method on the Properties of Amphotericin B−Dipalmitoyl Phosphatidic Acid Mixed Films at the Air/Water Interface

Abstract

Using two different spreading techniquesmixed spreading and separate spreadingand film surface pressure measurements, the mixing behavior of the amphotericin B (AmB)/dipalmitoyl phosphatidic acid (DPPA) system was investigated.The Π−A isotherms were found to exhibit various “plateaus” suggesting the occurrence of different phase transitions of the monolayer. On the basis of the surface phase rule, the phase diagram of mixed films was elucidated. The AmB molecule takes two orientations in the monolayer state, i.e., horizontal and vertical, depending on the surface pressure. Horizontally oriented AmB and vertically oriented phospholipid form a mixed monolayer that deviates from ideal behavior. On the other hand, vertically oriented AmB molecules were found to be immiscible with DPPA in a monolayer, although both molecules are normal to the surface and parallel to each other. The deviations from ideality can be ascribed to the formation of an AmB/DPPA complex of 2:1 stoichiometry as a result of the existence of hydrogen bonds and ionic attractive forces between polar groups of the two components.

Synthesis-enabled functional group deletions reveal key underpinnings of amphotericin B ion channel and antifungal activities

“…This would be consistent with the proposal that specific interactions between the charged functional groups of AmB and the zwitterionic PC headgroups (Fig. 1D) (15)(16)(17)(18)(19) help anchor AmB to the membrane (12,13). To test this proposal, we first determined the relative binding of AmB and its derivatives to yeast cells (58).…”

“…1C) (8,(11)(12)(13)(14). Second, one or both of these functional groups are proposed to form critical polar interactions with phospholipid headgroups either to "anchor" AmB to the membrane (12,13) and/or to promote channel formation (15)(16)(17)(18)(19) (Fig. 1D).…”

“…Despite more than half a century of intensive study, however, the mechanism of action of AmB is poorly understood. Even the most basic components of the leading model remain unclear, including the structure/function relationships that underlie channel self-assembly (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19), the importance of AmB/phospholipid interactions (12,13,(15)(16)(17)(18)(19), the role of membrane sterols in forming ion channels (5-13, 15, 20-40), and even whether channel formation is causitively linked to antifungal activity (41)(42)(43).…”

Interactions in Monolayers: A Study of the Behavior of Poly(methyl methacrylate)–Lysozyme Mixed Films from Surface Pressure–Area and Ellipsometric Measurements

“…Moreover, Fukuda et al attribute the negative deviations of poly(vinyl stearate)–hexadecanol mixed films to the packing of these compounds. In the same line, our studies on amphotetericin B (AmB)–phospholipids − and AmB–cholesterol , mixed films confirm the existence of a complex 2:1 (AmB/phospholipid or AmB/cholesterol), via the formation of hydrogen bonds between hydroxyl groups of the phospholipid (or cholesterol) and AmB, respectively, and via ionic interactions between the ionized phosphate groups of phospholipids and the positively charged groups of AmB, which explains the deviations from the ideal behavior of these systems.…”

Revealing the Orientation of Nystatin and Amphotericin B in Lipidic Multilayers by UV−Vis Linear Dichroism

“…Published papers on this subject are rare and mainly devoted to monolayers. [5][6][7][8][9][10][11][12][13][14]…”