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.
Colotto
A
A
Istituto di Scienze Fisiche, Facoltà di Medicina, Ancona, Italy.
Mariani
P
P
Ponzi Bossi
M G
MG
Rustichelli
F
F
Albertini
G
G
Amaral
L Q
LQ
D002151:Calorimetry; D005583:Fourier Analysis; D008051:Lipid Bilayers / Q000737:chemistry*; D008956:Models, Chemical; D015394:Molecular Structure; D010713:Phosphatidylcholines; D010869:Pindolol / Q000494:pharmacology*; D013696:Temperature; D014867:Water; D014961:X-Ray Diffraction
D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D014867:Water; D010869:Pindolol; C010942:1,2-distearoyllecithin