Hexadecylphosphocholine interaction with lipid monolayers

Abstract

The phospholipid analogue miltefosine or hexadecylphosphocholine (HePC) is a drug of high interest in the treatment for fatal visceral leishmaniasis (VL) due to Leishmania donovani particularly because of its activity by oral route. In this study, the interaction of HePC with a monolayer of beta-palmitoyl-gamma-oleyl-phosphatidylcholine (POPC) as membrane model or sterol (ergosterol or cholesterol) was investigated. At a constant pressure of 25 mN/m, the adsorption kinetics of HePC into the monolayers showed that HePC molecules are inserted into the monolayer of lipids as monomers until the critical micellar concentration (CMC). At HePC concentrations superior to the CMC, the micelles of HePC are deployed at the interface as groups of monomers into the POPC or sterol monolayer. The study of mixture of HePC/(POPC or sterol), spread at the air-water interface, shows that a simple miscibility between HePC and POPC is observed, whereas a high condensation appears between HePC and sterols showing a high affinity between HePC and sterols. In addition, HePC does not act as detergent disturbing membrane integrity.

Interaction of Alkylphospholipid Formulations with Breast Cancer Cells in the Context of Anticancer Drug Development

“…We can conclude from the above experiment that analkylphospholipid-like molecule can easily exchange between membranes and can accumulate in cells when they are in contact with liposomal OPP formulations. This is in agreement with lipid monolayer experiments, which showed that alkylphospholipids, below the critical micellar concentration (CMC), insert progressively into lipid monolayers as monomers from the aqueous medium, while above CMC, not only monomers but also groups of monomers (micelles) are transferred into the monolayers (Rakotomanga et al, 2004). It was also shown that, while the alkylphospholipid HePC is miscible with POPC, there is high affinity between HePC and sterols (ergosterol, and cholesterol) and that maximum condensation is reached at a ratio of HePC/sterol around 50:50 (mol/mol) (Rakotomanga et al, 2004).…”

“…This is in agreement with lipid monolayer experiments, which showed that alkylphospholipids, below the critical micellar concentration (CMC), insert progressively into lipid monolayers as monomers from the aqueous medium, while above CMC, not only monomers but also groups of monomers (micelles) are transferred into the monolayers (Rakotomanga et al, 2004). It was also shown that, while the alkylphospholipid HePC is miscible with POPC, there is high affinity between HePC and sterols (ergosterol, and cholesterol) and that maximum condensation is reached at a ratio of HePC/sterol around 50:50 (mol/mol) (Rakotomanga et al, 2004). This kind of behavior is generally known as the condensing effect of cholesterol towards phospholipids (Chapman et al, 1969;Ghosh & Tinoco, 1972).…”

“…4. While alkylphospholipid HePC is miscible with POPC, there is high affinity between HePC and sterols (ergosterol, and cholesterol) and that maximum condensation is reached at a ratio of HePC/sterol around 50:50 (mol/mol) (Rakotomanga et al, 2004). This kind of behavior is generally known as the condensing effect of cholesterol towards phospholipids (Chapman et al, 1969;Ghosh & Tinoco, 1972).…”

“…Its CMC is around 10 μM, while 14P (spin labeled OPP, containing the nitroxide group at the 14 th C atom) exhibited the CMC of around 200 μM (Mravljak et al, 2005). Edelfosine and OPP disperse in water in the form of micelles, due to their inverted-cone shape (Busto et al, 2007), displaying a CMC at 2.5 -3 μM (Rakotomanga et al, 2004). It appears that addition of the doxyl group to OPP distorts the inverted-cone shape of molecule to greater extent when it is placed further away from the polar head group, which results in increased CMC.…”

“…3. Lipid monolayer experiments showed that alkylphospholipids, below the critical micellar concentration (CMC), insert progressively into lipid monolayers as monomers from the aqueous medium, while above CMC, not only monomers but also groups of monomers (micelles) are transferred into the monolayers (Rakotomanga et al, 2004). 4.…”