Effect of Curcumin on the Diffusion Kinetics of a Hemicyanine Dye, LDS-698, across a Lipid Bilayer Probed by Second Harmonic Spectroscopy

The diffusion kinetics of a hemicyanine dye, LDS-698, across model membrane bilayers was studied in real time by the surface specific second harmonic technique. Using liposomes made from different headgroups, it has been established that the diffusion is initiated by electrostatic adsorption of the positively charged dye to the outer surface of negatively charged liposomes and its time constant is affected by the rigidity of the bilayer. In the presence of the liphophilic drug curcumin (curcumin/lipid mole ratio similar to 0.2), the diffusion of LDS-698 was observed to be faster by similar to 56 times (from 780 to 14 s) at 25 degrees C. Under similar curcumin concentration, when cholesterol containing liposomes are used at 2 degrees C, the observed diffusion time constant increases from 14 to 65 s, showing that the effect of curcumin is superior to the effect of increasing bilayer rigidity on the diffusion process. Control experiments with other lipophilic molecules such as DPH and Nile Red showed that the effect of liposomal curcumin is superior. Consistent with previous reports of curcumin affecting the bilayer organization, this study demonstrates increased permeability of liposomal curcumin, in particular against organic cations. It is speculated that origin of this enhanced membrane permeability by lipophilic molecules may depend upon the interaction of the molecule with the polar headgroup region of the lipid which, in turn, is expected to depend on the chemical structure of the molecule.