METHOTREXATE INTERACTION WITH A LIPID-MEMBRANE MODEL OF DPPC

Dipalmitoylphosphatidylcholine (DPPC) liposomes were employed as membr ane models for the investigation of the interaction occurring between methotrexate (MTX) and bilayer lipid matrix. Liposomes were obtained b y hydrating a lipid film with 50 mM Tris buffer (pH 7.4). The differen tial scanning calorimetry (DSC) evaluation of the thermotropic paramet ers associated with the phase transitions of DPPC liposomes gave usefu l information about the kind of drug-membrane interaction. The results showed an electrostatic interaction taking place with the negatively charged molecules of MTX and the phosphorylcholine head groups, consti tuting the outer part of DPPC bilayers. No interaction with the hydrop hobic phospholipid bilayer domains was detected, revealing a poor capa bility of MTX to cross through lipid membranes to reach the interior c ompartment of a lipid bounded structure. These findings correlate well with in vitro biological experiments on MTX cell susceptibility.