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|Type:||Artigo de periódico|
|Title:||Probing the Combined Effect of Flunitrazepam and Lidocaine on the Stability and Organization of Bilayer Lipid Membranes. A Differential Scanning Calorimetry and Dynamic Light Scattering Study|
de Paula, E
|Abstract:||Combined effects of flunitrazepam (FNZ) and lidocaine (LDC) were studied on the thermotropic equilibrium of dipalmitoyl phosphatidylcholine (dpPC) bilayers. This adds a thermodynamic dimension to previously reported geometric analysis in the erythrocyte model. LDC decreased the enthalpy and temperature for dpPC pre- and main-transitions (Delta H (p), Delta H (m), T (p), T (m)) and decreased the cooperativity of the main-transition (Delta T (1/2),(m)). FNZ decreased Delta H (m) and, at least up to 59 mu M, also decreased Delta H (p). In conjunction with LDC, FNZ induced a recovery of a dagger T (1/2,m) control values and increased Delta H (m) even above the control level. The deconvolution of the main-transition peak at high LDC concentrations revealed three components possibly represented by: a self-segregated fraction of pure dpPC, a dpPC-LDC mixture and a phase with a lipid structure of intermediate stability associated with LDC self-aggregation within the lipid phase. Some LDC effects on thermodynamic parameters were reverted at proper LDC/FNZ molar ratios, suggesting that FNZ restricts the maximal availability of the LDC partitioned into the lipid phase. Thus, beyond its complexity, the lipid-LDC mixture can be rationalized as an equilibrium of coexisting phases which gains homogeneity in the presence of FNZ. This work stresses the relevance of nonspecific drug-membrane binding on LDC-FNZ pharmacological interactions and would have pharmaceutical applications in liposomal multidrug-delivery.|
Thermotropic phase changes
|Editor:||Humana Press Inc|
|Appears in Collections:||Artigos e Materiais de Revistas Científicas - Unicamp|
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