LIPID DRUG-INTERACTION - A STRUCTURAL-ANALYSIS OF PINDOLOL EFFECTS ON MODEL MEMBRANES

The ternary system constituted by distearoylphosphatidylcholine, pindolol (a vasodilator drug) and water has been investigated by using X-ray diffraction and calorimetric techniques. The structural modifications induced by the drug have been determined and a possible interaction model has been derived. In particular, the pindolol content-temperature dependent phase diagram shows the occurrence of two new phases: the first is an interdigitated gel, and the second is a lamellar structure presenting an unusual mixed disordered-ordered conformation of the hydrocarbon chains (L(alpha-beta)). The comparative analysis of electron density profiles relative to the L(alpha-beta) phase, reveals significant modifications in the paraffinic region of the lipid layer. In agreement with thermodynamic results, the structural data suggest that the drug induces a stiffening and a tightening of the hydrocarbon chains. Moreover, the hydrophilic properties of the membrane (particularly in P(beta') and L(alpha-beta) phases) present an evident dependence with the drug concentration.