Effect of Bilayer Partitioning of Curcumin on the Adsorption and Transport of a Cationic Dye Across POPG Liposomes Probed by Second-Harmonic Spectroscopy

The effect of Curcumin partitioning into the bilayer during the adsorption and transport of a cationic dye, LDS, across a negatively charged POPG bilayer was investigated by the interface-selective second-harmonic (SH) spectroscopic technique. The intensity of SH electric field (E-2 omega) arising due to LDS adsorbed on the outer bilayer of the POPG liposome was observed to increase instantaneously (<1 s) following the addition of Curcumin. The fractional increase in the SH electric field (E-2 omega(f)) and the bilayer transport rates (kT) of LDS were studied with respect to the pH of the solution and also with the Curcumin content in the lipid bilayer. Results obtained indicate that compared with the anionic form of the drug, its neutral form is more conducive of increasing the Ef2? of LDS. With increasing Curcumin content in the lipid bilayer, two distinct regimes could be observed in terms of E-2 omega(f) and kT values of LDS. For Curcumin:Lipid (C/L) ratio =0.02, the E-2 omega(f) of LDS increases rapidly, while kT remains unchanged; and for C/L ratio =0.02, the E-2 omega(f) values remains more or less constant, while there is a significant (similar to 40 times) increase followed by a modest increase in the kT values of LDS. The observed results support an earlier two-state binding model of Curcumin with the POPG bilayer. In addition, it is further proposed that at low C/L ratio Curcumin binds to the surface of the bilayer replacing the counterions (Na+) bound to the lipid head groups, which changes the bilayer surface charge density, thereby causing more LDS cations to adsorb on the bilayer surface. At high C/L ratio, Curcumin intercalates within the hydrophobic domain of the bilayer, altering its hydrophobicity and inducing enhanced transport of the LDS cation. Results presented in this work provide further insights into how Curcumin alters bilayer properties when it partitions from the aqueous to the bilayer phase.