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 ofvarious cerebral diseases. To evaluate in vitro the possible in vivo interaction with biological membranes and to carryout a pre-formulation study for the realization of an idebenone-loaded liposome system, the interaction between thisdrug 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 noticeablyinfluenced the thermotropic behavior of the membranes, shifting the main transition peak temperature towards lowervalues and broadening the peak. The extent of the perturbation of the membrane properties is a function of thecontent of idebenone. In particular, beyond an idebenone molar fraction of 0.09 a phase segregation of the lipidcomponents constituting the bilayers was detected. These features showed that the drug is fully inserted into thebilayer matrix of the various membranes. The idebenone–membrane interaction is enhanced by the presence ofnegatively charged phospholipids. A kinetic experiment showed that the limiting step in the interaction with abiological substrate could be the diffusion process through the aqueous compartments rather than the interaction withthe biological membrane bilayers. The formulation of a liposomal drug delivery system containing idebenone mayimprove the pharmaceutical and therapeutic properties of the drug.