Olanzapine interaction with dipalmitoyl phosphatidylcholine (DPPC) and 1-palmitoyl-2-oleoyl phosphatidylserine (POPS) bilayer: A 13C and 31P solid-state NMR study

Abstract

Phospholipid bilayer interaction of olanzapine (OLZ), a thienobenzodiazepine derivative and an antipsychotic agent, has been studied with 13C and 31P solid-state NMR. A dipalmitoyl phosphatidylcholine (60%)/1-palmitoyl-2-oleoyl phosphatidylserine (40%) bilayer (DPPC(60%)/POPS(40%)) with 50 wt.% H 2O, with and without 10 mol% OLZ have been investigated. The results reveal that both the serine and the choline head groups are affected by OLZ interaction with the bilayer. The OLZ interaction with the serine and the choline head groups appears to be caused by electrostatic attraction to the serine head group carboxyl and repulsion of the choline head group positively charged nitrogen. 31P MAS NMR experiments show the appearance of two new 31P resonances both for the PS and the PC phosphorous in the presence of OLZ. Static 31P NMR spectra demonstrate a decrease in chemical shift anisotropy (CSA) of the OLZ containing bilayer when in the liquid-crystalline phase and an increase in CSA when in the gel state.