The effects of miltefosine on the structure and dynamics of DPPC and DPPS liposomes mimicking normal and cancer cell membranes: FTIR and DSC studies

Abstract

Miltefosine (MLT,hexadecylphosphocholine (HePC)) is an alkylphospholipid (APL) clinically used against leishmaniasis and the topical treatment of cancer. Although the MLT mechanism of action has not yet been clarified, it is thought to be related to its incorporation into the plasma membrane, affecting lipid homeostasis. An essential feature of APLs is that they possess a lethal effect that acts only on malignant cells without affecting normal cells; this property indicates the potential selective antitumor properties of these types of drugs. However, the exact mechanism of APLs action at the molecular level is not yet known in detail. This study aimed to elucidate the molecular mechanisms of the interaction of the antitumor alkylphospholipid drug miltefosine with molecular models of normal and cancer cell membranes. The interaction of MLT with dipalmitoyl phosphatidylcholine (DPPC) multilamellar liposomes (MLVs) mimicking normal cell membrane and dipalmitoyl phosphatidylserine (DPPS) multilamellar liposomes (MLVs) mimicking cancer cell membrane was studied in the presence of (1 mol%,3 mol%, 6 mol%, 9 mol%, 15 mol%, 24 mol%, 30 mol% and 35 mol%) and in the absence of MLT by using two different non-invasive techniques; Fourier Transform Infrared (FTIR) spectroscopy and Differential Scanning Calorimetry (DSC). The comparative results show that miltefosine affects DPPS/MLT systems modeled cancer cells more than the DPPC/MLT system modeled healthy cells. Our results may be proof at the molecular level that miltefosine has selective antitumor properties.