A calorimetric study on the idebenone-phospholipid membrane interaction

Idebenone is a drug acting at the level of the central nervous system and is largely employed in the treatment of various cerebral diseases. To evaluate in vitro the possible in vivo interaction with biological membranes and to carry out a pre-formulation study for the realization of an idebenone-loaded liposome system, the interaction between this drug and model membranes made up of various naturally occurring phospholipids was investigated. The idebenone– membrane interaction was studied by differential scanning calorimetry (DSC). The presence of the drug noticeably influenced the thermotropic behavior of the membranes, shifting the main transition peak temperature towards lower values and broadening the peak. The extent of the perturbation of the membrane properties is a function of the content of idebenone. In particular, beyond an idebenone molar fraction of 0.09 a phase segregation of the lipid components constituting the bilayers was detected. These features showed that the drug is fully inserted into the bilayer matrix of the various membranes. The idebenone–membrane interaction is enhanced by the presence of negatively charged phospholipids. A kinetic experiment showed that the limiting step in the interaction with a biological substrate could be the diffusion process through the aqueous compartments rather than the interaction with the biological membrane bilayers. The formulation of a liposomal drug delivery system containing idebenone may improve the pharmaceutical and therapeutic properties of the drug.