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

Rey-Gómez-Serranillos, I.; Dynarowicz-Łątka, Patrycja; Miñones, J.; Seoane, R.

doi:10.1006/jcis.2000.7310

Cited by 15 publications

(9 citation statements)

References 11 publications

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“…For mixtures with a higher proportion of AmB (>50%), the collapse pressure values cannot be exactly evaluated due to the dissolution of AmB in the subphase. 28,29 The above-mentioned phase transition can be more clearly seen in the plots of the compressional modulus as a function of the surface pressure (inset of Figure 3). A characteristic minimum (M) can be clearly seen in the C s -1 -π curves, which is equivalent to the pseudoplateau recorded in the π-A isotherms at 21 mN/m.…”

Section: Resultsmentioning

confidence: 86%

Amphotericin B−Dipalmitoyl Phosphatidyl Glycerol Interactions Responsible for the Reduced Toxicity of Liposomal Formulations: A Monolayer Study

et al. 2002

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Mixtures of amphotericin B (AmB) and dipalmitoyl phosphatidyl glycerol (DPPG) were studied as floating Langmuir monolayers at the air/water interface. The films were analyzed using surface pressure-area (π-A) isotherms and compressional modulus-surface pressure (Cs -1 -π) plots in addition to Brewster angle microscopy. The film components were found to interact with each other with the strongest interactions occurring at the ca. 2:1 AmB:DPPG mixed film composition (XAmB ) 0.66), suggesting the formation of stable complexes composed of two horizontally oriented AmB molecules and one vertically oriented DPPG molecule. It has been suggested that the interactions between AmB and the phospholipid may compete in vivo with those between the antibiotic molecules and cellular membrane sterols. The toxic effects of AmB formulations containing free AmB (Fungizone) are thought to be due to the presence of free drug molecules that can interact with cellular membrane sterols, forming channels responsible for the observed toxicity. In liposomal AmB formulations on the other hand, AmB molecules are "immobilized" by their interactions with liposomal phospholipids, and therefore, are not as toxic to host cells.

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Section: Resultsmentioning

confidence: 86%

Amphotericin B−Dipalmitoyl Phosphatidyl Glycerol Interactions Responsible for the Reduced Toxicity of Liposomal Formulations: A Monolayer Study

et al. 2002

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“…Indeed, at π ) 30 mN/m, both the additivity of the molecular areas and the nearly constant values of the transition surface pressures (Table 1) indicate the immiscibility between AmB and DPPC under these conditions, although in this situation the values for the molecular area of AmB are uncertain, due to the instability of the AmB monolayer. 51- 53 On the other hand, at surface pressures below that for the transition M, the existence of attractive interactions might be expected, due to the formation of the 2:1 (AmB/ DPPC) complex that could provoke the condensation of the film components at the surface and thus the occurrence of negative deviations from ideal behavior. However, the experimental results (Figure 8) show the existence of positive deviations.…”

Section: Miscibility Of the Complex With An Excess Of Particular Compmentioning

confidence: 96%

Mixed Monolayers of Amphotericin B−Dipalmitoyl Phosphatidyl Choline: Study of Complex Formation

Miñones¹,

Conde²,

Patino³

et al. 2002

Langmuir

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Mixed Langmuir monolayers of amphotericin B (AmB) and dipalmitoyl phosphatidyl choline (DPPC) were investigated by recording surface pressure-area (π-A) isotherms in addition to Brewster angle microscopy. The analyses of π-A and compressional modulus curves indicate the existence of interactions in the AmB-DPPC system; the greatest were found to occur for a ca. 2:1 AmB/DPPC mixture. For this mixed monolayer (XAmB ) 0.66), the formation of a stable complex, composed of two horizontally oriented AmB molecules and one DPPC molecule in a vertical position, is suggested. For mixtures containing AmB in excess as compared to the stoichiometric mixture for the complex formation (XAmB > 0.66), the filmforming components are miscible and the mixed monolayer consists of AmB-DPPC complexes together with horizontally (at surface pressures below the first transition) or vertically (at pressures above this transition) oriented free AmB molecules. On the other hand, mixtures of AmB-DPPC complex and DPPC in excess (at XAmB < 0.66) were found to be miscible at surface pressures below the second transition. However, the system becomes immiscible at higher surface pressures.

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“…During the compression of the monomolecular layer of AmB and AmB–Cu 2+ , the organization of the molecules on the surface is altered, which is manifested in the occurrence of a characteristic broad plateau. The presence of the plateau is interpreted as progressive changes in the orientation of AmB molecules caused by compression from the horizontal in an expanded state to vertical position in a liquid-condensed phase and also desorption of molecules from the surface. − It was confirmed that this plateau transition depends on temperature, and the surface pressure value of it decreases with increasing temperature . As for the parental molecule AmB, the AmB–Cu 2+ complex could assume two different positions at the interface, depending on the orientation of its long polyene axis: parallel to the interface or perpendicular to it.…”

Section: Resultsmentioning

confidence: 92%

“…In our opinion, the negative deviations in the case of AmB are not due to a condensation and intermolecular attractions, but are rather caused by the expelling of molecules from monolayer during reorientation process, which leads to a reduction in the mean area per molecule. Effectively, at π > 5 mN/m, AmB molecules were to be found in the oblique form, and some of the hydrogen bonds were broken, facilitating desorption of antibiotic from the interface . For the higher surface pressure value (15 mN/m), only a slight negative deviation from ideality was noted.…”

Section: Resultsmentioning

confidence: 99%

“…Effectively, at π > 5 mN/m, AmB molecules were to be found in the oblique form, 37 and some of the hydrogen bonds were broken, facilitating desorption of antibiotic from the interface. 30 For the higher surface pressure value (15 mN/m), only a slight negative deviation from ideality was noted. The experimental points nearly coincide with the values calculated according to the additivity rule (marked as dashed lines) with only a negligible positive deviation for X AmB > 0.7.…”

Section: Methodsmentioning

confidence: 91%

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Effect of the Amphotericin B and Its Copper Complex on a Model of the Outer Leaflet of Human Erythrocyte Membrane

2016

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A comparative study on the effect of an antibiotic amphotericin B (AmB) and its copper complex on the multicomponent monolayers imitating the outer leaflet of human erythrocyte membrane has been performed by means of the Langmuir monolayer technique. The properties of mixed films were analyzed by thermodynamic description of the interactions between the molecules complemented with the morphology of monolayers established by Brewster angle microscopy (BAM). The results revealed differences in the molecular organization of the two antibiotic forms at the air/water interface, which were explained by the different spatial structure of the complex. The lipophilicity of the complex contributed to considerably more effective interactions with the components of the model membrane, compared to pure antibiotic, expressed by negative values of the excess of free energy of mixing ΔG in the whole range of mole fractions. The mixed films with AmB were more stable as the proportion of lipids in the mixture increased. BAM images demonstrated that the addition of antibiotic at high content into the lipid mixture led to the formation of crystallite structures within the film, probably caused by the expelling of AmB molecules from mixed monolayers. These findings could help to explain the mechanism of the hemolytic activity of polyene antibiotics.

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

Cited by 15 publications

References 11 publications

Amphotericin B−Dipalmitoyl Phosphatidyl Glycerol Interactions Responsible for the Reduced Toxicity of Liposomal Formulations: A Monolayer Study

Amphotericin B−Dipalmitoyl Phosphatidyl Glycerol Interactions Responsible for the Reduced Toxicity of Liposomal Formulations: A Monolayer Study

Mixed Monolayers of Amphotericin B−Dipalmitoyl Phosphatidyl Choline: Study of Complex Formation

Effect of the Amphotericin B and Its Copper Complex on a Model of the Outer Leaflet of Human Erythrocyte Membrane

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