Miltefosine and BODIPY-labeled alkylphosphocholine with leishmanicidal activity: Aggregation properties and
Marina Berardi Barioni1, Ana Paula Ramos2, Maria Elisabete Darbello Zaniquelli2
1Departamento de Física, FFCLRP, Universidade de São Paulo, Bandeirantes Avenue 3900, 14040-901 Ribeirão Preto, São Paulo, Brazil.
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.
Insights
Miltefosine (MT) effectively treats leishmaniasis. Understanding its aggregation and lipid interactions is key to improving drug delivery and efficacy, revealing how it forms aggregates with lipids above its critical micelle concentration.
Area of Science:
- Pharmacology
- Biochemistry
- Physical Chemistry
Background:
- Miltefosine (hexadecylphosphocholine, MT) is an effective oral treatment for leishmaniasis.
- Understanding MT's aggregation and lipid interactions is crucial for optimizing its pharmacokinetics, bioavailability, and antiparasitic activity.
Purpose of the Study:
- To investigate the aggregation behavior of Miltefosine in aqueous solutions.
- To characterize the interaction of Miltefosine with lipid vesicles.
Main Methods:
- Surface tension measurements to determine critical micelle concentration (CMC).
- Fluorescence spectroscopy to monitor Miltefosine aggregation and its effects on lipid vesicles.
Main Results:
- The critical micelle concentration (CMC) of Miltefosine was determined to be 50μM in buffered water, influenced by salt concentration.
- Miltefosine induced minor changes on the vesicle surface below CMC, primarily through bilayer disordering.
- Above CMC, Miltefosine formed mixed aggregates with lipids and probes, significantly altering vesicle structure, with diminished effects in less ordered lipid bilayers.
Conclusions:
- Miltefosine's aggregation properties are concentration-dependent and influenced by environmental factors like salt.
- Miltefosine's interaction with lipid membranes is complex, leading to aggregate formation that impacts its behavior and potential efficacy.
- These findings provide insights into Miltefosine's physicochemical properties relevant to its therapeutic application in leishmaniasis.
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