Effect of amphotericin B on dipalmitoylphosphatidylcholine membranes: calorimetry, ultrasound absorption and monolayer technique studies.
Amphotericin B (AmB) is a popular drug frequently applied in the treatment of mycosis. Differential scanning calorimetry (DSC), ultrasound absorption and monomolecular layer technique were applied to study the effect of AmB on organisation of dipalmitoylphosphatidylcholine (DPPC) membranes. DSC-determined enthalpy of the main phase transition of DPPC liposomes was found to be a sensitive parameter to monitor AmB-DPPC interaction. The enthalpy of the phase transition decreases with the increase in molar fraction of AmB incorporated to membranes. The exceptionally sharp decrease in the enthalpy of the transition was observed in the membranes containing 5-7 mol% AmB. Ultrasound absorption-monitored main phase transition of DPPC is very broad under the presence of 5 mol% AmB showing destabilisation and disorganisation of a membrane structure. These findings are discussed in comparison to monomolecular layer study of two-component DPPC-AmB system. Analysis of the surface pressure-molecular area isotherms of compressing DPPC-AmB films at the air-water interface shows pronounced increase in mean molecular area at AmB concentrations corresponding to those found to destabilise DPPC membranes of liposomes. Disorganisation of lipid bilayers due to the presence of AmB in concentrations below 10 mol% with respect to lipid is discussed in terms of toxicity and side effects of this drug.
Wójtowicz
K
K
Department of Biophysics, Medical Academy, Lublin, Poland.
Gruszecki
W I
WI
Walicka
M
M
Barwicz
J
J
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry*; D000666:Amphotericin B / Q000737:chemistry*; D000935:Antifungal Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D013816:Thermodynamics; D014465:Ultrasonics
D000935:Antifungal Agents; D015060:1,2-Dipalmitoylphosphatidylcholine; D000666:Amphotericin B