Different effects of two structurally similar carotenoids, lutein and β-carotene, on the thermotropic behaviour of phosphatidylcholine liposomes.: Calorimetric evidence of their hindered transport through biomembranes

The effect exerted by two structurally similar carotenoids, lutein and beta-carotene, possessing antioxidant activity on the thermotropic behavior of model membranes constituted by dimyristoylphosphatidylcholine (DMPC) multilamellar vesicles, was studied by differential scanning calorimetry (DSC). Attention was directed to evaluating eventual modifications in drug-lipid interaction induced by drug structure. The two compounds examined, when dispersed in liposomes during their preparation, were found to modify the gel-to-liquid crystal phase transition of DMPC vesicles differently. Only the lutein caused a large effect on the transition temperature (T(m)), shifting it toward lower values and decreasing the enthalpy (Delta H) associated with the L(beta) - L(alpha) lipidic phase transition. These modifications were a function of the drug concentration, and modulated by the different polarity induced by the presence of hydroxyl groups in the terminal aromatic rings. By carrying out a different liposomes loading procedure, namely putting solid carotenoids and MLV or LUV aqueous dispersions in contact and leaving these mixtures for long incubation times at temperatures higher than transitional lipid temperatures, no interaction was detected for both the carotenoids with lipid vesicles, implying a hindered transfer of the carotenoids through the aqueous medium. Also, the drugs transfer from carotenoid-loaded MLV to empty vesicles was studied and no effect was detected on the empty membranes. The results can be explained in terms of compound hydrophobicity which allows the membrane interaction with carotenoids and, at thr: same time, a low water solubility which avoids the transfer through the aqueous medium as well as the matching of the hydrocarbons chains of the carotenoid between lipid bilayer chains, suggesting a relation between drugs structure, bilayer thickness and membrane interaction. (C) 1999 Elsevier Science B.V. All rights reserved.