Miltefosine and BODIPY-labeled alkylphosphocholine with leishmanicidal activity: Aggregation properties and interaction with model membranes

Miltefosine (hexadecylphosphocholine, MT) afforded successful oral treatment against human visceral and cutaneous leishmaniasis. Knowledge of MT aggregation in aqueous solutions and of its interaction with lipid membranes is important to understand pharmacokinetics, bioavailability and antiparasitic...

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Published in:	Biophysical chemistry Vol. 196; pp. 92 - 99
Main Authors:	Barioni, Marina Berardi, Ramos, Ana Paula, Zaniquelli, Maria Elisabete Darbello, Acuña, Alberto Ulises, Ito, Amando Siuiti
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier B.V 01-01-2015
Subjects:	Antiparasitic Agents - chemistry Antiparasitic Agents - metabolism Azoles - chemistry BODIPY-alkylphosphocholine Boron Compounds - chemistry Critical micelle concentration (CMC) Human leishmaniasis Humans Leishmanicidal drug Nitrobenzenes - chemistry Phosphorylcholine - analogs & derivatives Phosphorylcholine - chemistry Phosphorylcholine - metabolism Spectrometry, Fluorescence Surface Tension Unilamellar Liposomes - chemistry Unilamellar Liposomes - metabolism Critical micelle concentration (CMC) Human leishmaniasis Leishmanicidal drug BODIPY-alkylphosphocholine
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Summary:	Miltefosine (hexadecylphosphocholine, MT) afforded successful oral treatment against human visceral and cutaneous leishmaniasis. Knowledge of MT aggregation in aqueous solutions and of its interaction with lipid membranes is important to understand pharmacokinetics, bioavailability and antiparasitic effects. Methods based on surface tension and fluorescence spectroscopy gave the value of 50μM for critical micelle concentration (CMC) in buffered water solution, and the value is influenced by salt content. Interaction between MT and lipid vesicles was monitored by fluorescence and the drug promotes only minor changes in the surface of the vesicles. At MT concentration below CMC, modifications in probe fluorescence are due to disordering effects promoted by the drug in the bilayer. Above the CMC, MT promoted large modifications in the vesicles as a whole, resulting in mixed aggregates containing lipids, drug and probe. Effects are less evident above thermal phase transition when the bilayer is in less ordered state. [Display omitted] •From different methods, miltefosine CMC in aqueous solution was determined as 50μM.•Below CMC, miltefosine promotes fluidization of DMPC and DPPC unilamellar vesicles.•In the critical micelle concentration miltefosine causes loss of vesicles integrity.•Above CMC, mixed aggregates made of lipids, drug and fluorescent probe are formed.•The fluorescent analogue MT-EtBDP shows drug pronounced effects in the bilayer core.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0301-4622 1873-4200
DOI:	10.1016/j.bpc.2014.10.002