Chemistry and Physics of Lipids
95 (1998) 37–47
Lipid-drug interaction: thermodynamic and structural effects of
antimicotic fluconazole on DPPC liposomes
Annarina Ambrosini
a
, Guido Bossi
b
, Silvia Dante
c
, Bruno Dubini
c
, Luigi Gobbi
c
,
Luciana Leone
d
, Maria Grazia Ponzi Bossi
c,
*, Giovanna Zolese
a
a
Istituto di Biochimica, Facolta ` di Medicina, Uniersita ` di Ancona, Via Ranieri 65, 60131, Ancona, Italy
b
Clinica Dermatologica, Facolta ` di Medicina, Uniersita ` di Ancona, Via Ranieri 65, 60131, Ancona, Italy
c
Istituto di Scienze Fisiche and INFM unit of Ancona, Facolta ` di Medicina, Uniersita ` di Ancona, Via Ranieri 65, 60131,
Ancona, Italy
d
Istituto di Scienze Biomediche, Facolta ` di Medicina, Uniersita ` di Ancona, Via Ranieri 65, 60131, Ancona, Italy
Received 27 March 1998; received in revised form 12 June 1998; accepted 23 June 1998
Abstract
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 P
,
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. © 1998 Elsevier Science Ireland Ltd.
All rights reserved.
Keywords: Fluconazole; Model Membranes; DSC; X-ray diffraction; Transmission Electron Microscopy; Fluores-
cence
1. Introduction
Fluconazole [(difluoro-2,4-phenyl)-2-bis(1H -tri-
azole-1,2)-4-yl-1)-1,3-propanol-2] (Fig. 1) is a bis-
triazole compound which exhibits a broad
* Corresponding author. Tel.: +39 71 2204606; fax: +39
71 2204605; e-mail: FISMED@POPCSI.UNIAN.IT
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