MEMBRANE FLUIDIZATION BY ANIMYCOTIC BIFONAZOLE

Calorimetry, nuclear magnetic resonance and X-ray diffraction techniqu es have been used to obtain thermodynamic and structural information o n dipalmitoyl phosphatidylcholine (DPPC) liposomes doped by the antimy cotic drug bifonazole in the range O < R < 1, where R = moles of bifon azole/moles of DPPC. The technique of spin labeling electron spin reso nance (ESR) has also been used to study permeability and fluidity prop erties. The decrease of the cooperativity at the gel to liquid crystal line phase transition, as shown by ESR an DSC measurements, indicates that bifonazole imparts higher fluidity to the lipid matrix. Increase in permeability of ascorbate ions, after incorporation of bifonazole i n the membrane, has been detected by ESR experiments using spin label 5-SASL. (13)CNMR spectra indicate that the drug molecule is highly imm obilized. X-ray diffraction and freeze fracture TEM results show that the equilibrated phase at room temperature is lamellar and unidimensio nal together with the presence of small particles and pits of uniform size. A marked hysteresis is evident in the formation of this phase.