Lipid-drug interaction: thermodynamic and structural effects of antimicotic fluconazole on DPPC liposomes

Calorimetry, X-ray diffraction, transmission electron microscopy and fluorescence techniques have been used to obtain thermodynamic and structural information on dipalmitoyl phosphatidyl choline (DPPC) liposomes doped by the drug fluconazole. The decrease of the gel to liquid crystalline phase transition temperature, as shown by DSC measurements, indicates that fluconazole imparts higher fluidity to the lipid matrix. X-ray diffraction and freeze fracture results show that the presence of the drug stabilizes the two-dimensional lamellar rippled phase Pp., prolonging its range of existence, till to room temperature. Fluorescence data show that fluconazole could increase the polarity of fluorescence probe microenvironment. Thus, all the data ensure that fluconazole affects the lipid membrane properties and support the hypothesis that antifungal fluconazole activity is related not only to its structural characteristics but also to its ability to interact with the lipid bilayer. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.