Interaction of Adriamycin and N-Trifluoroacetyladriamycin-14-Valerate with Cardiolipin-Containing Lipid Bilayers

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Abstract
The interaction of adriamycin (ADR) and N-Trifluoroacetyladriamycin-14-valerate (AD 32) with cardiolipin (CL)-containing multilamellar vesicles was studied by high-sensitivity differential scanning calorimetry, using liposomes formed from either dipalmitoylphosphatidylcholine (DPPC) or dipalmitoylphosphatidylglycerol (DPPG) containing small amounts of CL. the drugs partitioned into cardiolipin-containing neutral and acidic bilayers in a manner similar to that observed earlier with CL-free bilayers. the partition coefficient of adriamycin in bilayers of vesicles prepared from DPPG or DPPG in admixture with CL was much higher than that obtained with neutral DPPC vesicles or the DPPC together with CL. Under all conditions, AD 32 was essentially completely partitioned into the lipid phase of the investigated phospholipid membranes. As expected, addition of adriamycin to CL-containing vesicles did not significantly change the thermotropic behavior of these bilayers, whereas the fluidizing effect of AD 32 was directly related to the CL content of the vesicles. the multipeak transitions produced by the anthracyclines in pure DPPG bilayers were preserved in the presence of CL, but the endotherms were broader and slightly shifted to lower temperatures, a finding indicative of stronger interactions. Chlorpromazine (CPZ), which was used as a reference compound to compare the effects produced by the anthracyclines, was found to behave similarly to AD 32 and to be more effective than quinidine (QND), in agreement with their behavior in CL-free liposomes.