Preparation and thermal behavior of liposomal nanoparticles incorporating bioactive labdane epimers

Lipophilic labdane type epimers 1 (5αH,9αH,13βH,10βMe-labda-8α-17diol) and 2 (5αH,9αH,13βH,10βMe - labda-8α-17diol) were isolated from Oxylobus glanduliferus. Their partitioning into model lipid membranes composed of Dipalmitoylphosphatidylcholine (DPPC) / Dipalmitoylphosphatidylglycerol (DPPG) (9:1 molar ratio) may induce membrane structure modifications. Differential Scanning Calorimetry (DSC) was used for elucidating the thermodynamic profile of the modifications induced in DPPC/DPPG bilayers after incorporating increasing concentrations of 1 or 2 by measuring calorimetric parameters. The epimers 1 and 2 showed thermal effects on the lipid bilayers composed of DPPC/DPPG in a manner depending on the concentration of 1 or 2. The decrease of the lipid bilayer cooperativity and the existence of interdigitated domains in the DPPC/DPPG bilayer were observed, studied and discussed. The different stereochemistry of the C-13 of 1 and 2 affected the structural order of lipid bilayers. The epimers 1 and 2 were incorporated into liposomal Small Unilamellar Vesicles (SUVs) composed of DPPC/DPPG. Their physicochemical stability was monitored over time under storage at 4 °C while the physicochemical stability of liposomes was strongly influenced by the negative charge of the liposomal vesicles.