title: Miltefosine and BODIPY-labeled alkylphosphocholine with leishmanicidal activity: Aggregation properties and interaction with model membranes.
abstract: 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.
authors.affiliation: Departamento de Física, FFCLRP, Universidade de São Paulo, Bandeirantes Avenue 3900, 14040-901 Ribeirão Preto, São Paulo, Brazil.
authors.forename: Marina Berardi
authors.initials: MB
authors.lastname: Barioni
authors.affiliation: Departamento de Química, FFCLRP, Universidade de São Paulo, Bandeirantes Avenue 3900, 14040-901 Ribeirão Preto, São Paulo, Brazil.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Ramos
authors.affiliation: Departamento de Química, FFCLRP, Universidade de São Paulo, Bandeirantes Avenue 3900, 14040-901 Ribeirão Preto, São Paulo, Brazil.
authors.forename: Maria Elisabete Darbello
authors.initials: ME
authors.lastname: Zaniquelli
authors.affiliation: Instituto de Química Física "Rocasolano", C.S.I.C., Serrano 119, E-28006 Madrid, Spain.
authors.forename: Alberto Ulises
authors.initials: AU
authors.lastname: Acuña
authors.affiliation: Departamento de Física, FFCLRP, Universidade de São Paulo, Bandeirantes Avenue 3900, 14040-901 Ribeirão Preto, São Paulo, Brazil. Electronic address: amandosi@ffclrp.usp.br.
authors.forename: Amando Siuiti
authors.initials: AS
authors.lastname: Ito
mesh_terms: D000977:Antiparasitic Agents / Q000737:chemistry* / Q000378:metabolism; D001393:Azoles / Q000737:chemistry; D001896:Boron Compounds / Q000737:chemistry*; D006801:Humans; D009578:Nitrobenzenes / Q000737:chemistry; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013500:Surface Tension; D053835:Unilamellar Liposomes / Q000737:chemistry / Q000378:metabolism
chemical_list: C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; C510797:7-nitrobenz-2-oxa-1,3-diazol-4-yl; D000977:Antiparasitic Agents; D001393:Azoles; D001896:Boron Compounds; D009578:Nitrobenzenes; D053835:Unilamellar Liposomes; D010767:Phosphorylcholine; C039128:miltefosine
keywords: BODIPY-alkylphosphocholine; Critical micelle concentration (CMC); Human leishmaniasis; Leishmanicidal drug