The influence of subphase temperature on miltefosine-cholesterol mixed monolayers.

Effects of the subphase temperature on the surface pressure (pi)-area (A) isotherms of mixed monolayers of miltefosine (hexadecylphosphocholine), a potential anticancer drug, and cholesterol were investigated at the air/water interface, which were supplemented with Brewster angle microscopy (BAM) observations. Comparison of the collapse pressure values, mean molecular areas, excess areas and excess free energy of mixing between the mixed monolayer at various molar ratios and the pure component monolayers showed that, regardless of the subphase temperature, the investigated miltefosine-cholesterol system is much more stable than that the pure component monolayers, suggesting strong attractive interactions between miltefosine and cholesterol in mixed monolayers. As a consequence, it was postulated that stable "complexes" of the two components could form at the interface, for which stoichiometry may vary with the subphase temperature. Such "surface complexes" should be responsible for the contraction of the mean molecular area and thus the high stability of the mixed monolayer.

Surface behavior of oleoyl palmitoyl phosphatidyl ethanolamine (OPPE) and the characteristics of mixed OPPE-miltefosine monolayers.

Langmuir monolayers of oleoyl palmitoyl phosphatidyl ethanolamine (OPPE) were investigated at the air/water interface by means of surface pressure (pi)-area (A) isotherms complemented with Brewster angle microscopy images upon film compression/expansion. The characteristic phase transition appearing in the course of pi/A isotherms was attributed to the coexistence of two liquid-expanded phases of different molecular ordering. The interactions between OPPE and hexadecylphosphocholine (miltefosine) were studied at different subphase pHs (2, 6, and 10) at 20 degrees C and analyzed with mean molecular area (A12)-, excess area of mixing (Aexc)-, and excess free energy of mixing (DeltaGexc)-composition plots. The obtained results indicate that at pH 10, where both OPPE and miltefosine polar groups are negatively charged, attractive interactions are observed (reflected by negative deviations from ideality), contrary to expectation. This peculiar behavior is explained as being due both to water molecules, which surround negatively charged polar groups and increase the distance between them, weakening in this way the electrostatic repulsion forces; and to positively charged counterions present in the diffuse double layer, neutralizing their charge. In this way, the van der Waals attraction forces between hydrocarbon tails of both molecules predominate and are responsible for the observed negative deviations from ideal behavior. Similar explanations are given for the observed negative deviations at pH 2 where both polar groups are positively charged. At pH 6, the observed negative deviations at low surface pressures and positive deviations at high pressures are interpreted as being due to a change in orientation of polar groups upon monolayer compression.

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

The desorption of amphotericin B (AmB) from mixed monolayers with cholesterol was studied by monitoring temporal changes in the relative area (A(t)/A(0)) as a function of time at constant surface pressures, corresponding to three distinct regions of the AmB isotherm. The loss of AmB molecules from the interface was found to obey the Ter Minassian Saraga model [J. Colloid Interface Sci. 11, 398 (1956)]. In the low surface pressure region the overall process of desorption is controlled by a one-step dissolution (at small times) followed by diffusion. At high pressures, however, the process of dissolution is more complex and consists of two steps that differ in rate. The presence of cholesterol molecules in the monolayer prevents the desorption of AmB molecules as evidenced by the constant desorption values. The analysis of the kinetics parameters confirms our previous findings, based on the analysis of excess functions, that the highest interactions, due to the stable complex formation, appear for the mixture of X(AmB)=0.7. Copyright 2001 Academic Press.