IIBYT   23944
INSTITUTO DE INVESTIGACIONES BIOLOGICAS Y TECNOLOGICAS
Unidad Ejecutora - UE
artículos
Título:
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
Autor/es:
CARUSO B; SANCHEZ JM; GARCIA DA; DE PAULA E.; PERILLO MA
Revista:
CELL BIOCHEMISTRY AND BIOPHYSICS
Editorial:
HUMANA PRESS INC
Referencias:
Lugar: Oregon; Año: 2013 vol. 66 p. 461 - 475
ISSN:
1085-9195
Resumen:
Combined effects of flunitrazepam and lidocaine 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. Lidocaine decreased the enthalpy and temperature for dpPC pre- and main- transitions (DHp,DHm,Tp,Tm) and decreased the cooperativity of the main transition (DT1/2,m). Flunitrazepam decreased DHm and, at least up to 59 uM, also decreased DHp. In conjunction with lidocaine, flunitrazepam induced a recovery of ∆T1/2,m control values and increased DHm even above the control level. The deconvolution of the main transition peak at high lidocaine concentrations revealed three components possibly represented by: a self-segregated fraction of pure dpPC, a dpPC-lidocaine mixture and a phase with a lipid structure of intermediate stability associated with lidocaine self-aggregation within the lipid phase. Some lidocaine effects on thermodynamic parameters were reverted at proper lidocaine/ flunitrazepam molar ratios, suggesting that flunitrazepam restricts the maximal availability of the lidocaine partitioned into the lipid phase. Thus, beyond its complexity, the lipid-lidocaine mixture can be rationalized as an equilibrium of coexisting phases which gains homogeneity in the presence of flunitrazepam. This work stresses the relevance of nonspecific drug-membrane binding on lidocaine-flunitrazepam pharmacological interactions and would have pharmaceutical applications in liposomal multidrug-delivery.