Permeation of Amphipathic Drug through a Lipid Bilayer: Curcumin

Abstract

Curcumin is a natural compound extracted from rhizomes of turmeric and is an example of amphipathic drug that bind to cell membranes. Extensive research over the last 50 years indicated that curcumin has antiinfammatory, antiangiogenic, antioxidant, wound-healing, and anticancer effects. The ability of drugs to permeate through membrane is very important to drug delivery. Passive transmembrane permeability is a major mechanism for drug absorption. In this study we used the aspirated GUV method to study how curcumin molecules permeate through a lipid membrane. Previous equilibrium studies showed that curcumin has two bound states on a lipid bilayer: one on the headgroup-chain interface (S) and another in the hydrocarbon chain region (I). The I state energy is significantly higher than the S state, so that initially as curcumin diffuse to the bilayer binds almost exclusively in the S state. Because of the existence of the I state, curcumin in the S state can translocate through the hydrocarbon barrier. We proved by the quenching ability of curcumin on lipid dye that, when the concentration is lower than the critical concentration, curcumin molecules which initial binding to the outer-layer can translocate into the inner-layer. The translocated molecules will then desorb from the inner layer thus permeate through membrane into the vesicle. We proved by content dye that below the critical concentration curcumin permeate through the membrane without making leakage. Surprisingly we found that when the concentration is higher than the critical concentration, the bilayer leaks dye molecules, thus further increases the permeation rate. Thus our results suggest that when a lipid bilayer is stretched beyond a certain limit by molecular binding, it might become leaky to small molecules. We believe that this complicated concentration-dependent permeation rate could be a common pattern for amphipathic drugs.