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. Trabajo Enviado con primera autoria compartida

CARUSO, B; J. M. SANCHEZ; DA GARCIA; DE PAULA E.; MA PERILLO

CELL BIOCHEMISTRY AND BIOPHYSICS

HUMANA PRESS INC

Lugar: Oregon; Año: 2012

1085-9195

Trabajo Enviado para su publicación con primera autoria compartida:Combined effects of flunitrazepam and lidocaine were studied on the thermotropicequilibrium of dipalmitoyl phosphatidylcholine (dpPC) bilayers. This adds a thermodynamicdimension to previously reported geometric analysis in the erythrocyte model. Lidocainedecreased the enthalpy and temperature for dpPC pre- and main- transitions (ΔHp,ΔHm,Tp,Tm)and decreased the cooperativity of the main transition (ΔT1/2,m). Flunitrazepam decreasedΔHm and, at least up to 59 uM, also decreased ΔHp. In conjunction with lidocaine,flunitrazepam induced a recovery of ΔT1/2,m control values and increased DHm even above thecontrol level. The deconvolution of the main transition peak at high lidocaine concentrationsrevealed three components possibly represented by: a self-segregated fraction of pure dpPC, adpPC-lidocaine mixture and a phase with a lipid structure of intermediate stability associatedwith lidocaine self-aggregation within the lipid phase. Some lidocaine effects onthermodynamic parameters were reverted at proper lidocaine/ flunitrazepam molar ratios,suggesting that flunitrazepam restricts the maximal availability of the lidocaine partitionedinto the lipid phase. Thus, beyond its complexity, the lipid-lidocaine mixture can berationalized as an equilibrium of coexisting phases which gains homogeneity in the presenceof flunitrazepam. This work stresses the relevance of nonspecific drug-membrane binding onlidocaine-flunitrazepam pharmacological interactions and would have pharmaceuticalapplications in liposomal multidrug-delivery.