Influence of the leprosy drug, dapsone on the model membrane dipalmitoyl phosphatidylethanolamine

Abstract: The influence of the sulfone drug, diamino diphenyl sulfone (DDS or dapsone) on the phase transitions and dynamics of the model membrane, dipalmitoyl phosphatidylethanolamine (DPPE)–water/buffer has been studied using DSC and (1H and 31P) NMR. These investigations were carried out with DPPE dispersion in both multilamellar vesicular (MLV) and unilamellar vesicular (ULV) forms for DDS/DPPE molar ratio, R, in the range 0–0.5. DSC results indicate that the mechanism by which DDS interacted with the DPPE membrane is independent of the morphological organization of the lipid bilayer and the solvent (water or buffer) used to form the dispersion. DDS affected both the thermotropic phase transitions and the molecular mobility of the DPPE membrane. Addition of increasing amounts of DDS to the DPPE dispersion, resulted in the lowering of the gel to liquid–crystalline phase transition temperature (T m) hence increased membrane fluidity. At all concentrations, the DDS is located close to the interfacial region of the DPPE bilayer but not in the acyl chain region. The interesting finding with MLV is that the gel phase of DPPE–water/buffer both in presence and absence of DDS, on prolonged equilibration at 25°C, transforms to a stable crystalline subgel phase(s). The DPPE–water system forms both crystalline subgel LLC (with transition temperature T LC < T m) and LHC (with transition temperature T HC ≥ T m) phases, while the DPPE–buffer system forms only subgel LLC phase. The presence of the drug seems to (i) increase the strength of the subgel LLC phase and (ii) decrease the strength of subgel LHC (for R <0.5) phase. However, the value of the transition temperatures T LC and T HC does not change significantly with increasing drug concentration. [Copyright &y& Elsevier]