Different effects of two structurally similar carotenoids, lutein and beta-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) multil amellar vesicles, was studied by differential scanning calorimetry (DSC). A ttention was directed to evaluating eventual modifications in drug-lipid in teraction induced by drug structure. The two compounds examined, when dispersed in liposomes during their prepar ation, were found to modify the gel-to-liquid crystal phase transition of D MPC vesicles differently. Only the lutein caused a large effect on the tran sition temperature (T-m), shifting it toward lower values and decreasing th e enthalpy (Delta H) associated with the L-beta - L-alpha lipidic phase tra nsition. These modifications were a function of the drug concentration, and modulated by the different polarity induced by the presence of hydroxyl gr oups in the terminal aromatic rings. By carrying out a different liposomes loading procedure, namely putting sol id carotenoids and MLV or LUV aqueous dispersions in contact and leaving th ese mixtures for long incubation times at temperatures higher than transiti onal lipid temperatures, no interaction was detected for both the carotenoi ds with lipid vesicles, implying a hindered transfer of the carotenoids thr ough the aqueous medium. Also, the drugs transfer from carotenoid-loaded ML V to empty vesicles was studied and no effect was detected on the empty mem branes. The results can be explained in terms of compound hydrophobicity wh ich allows the membrane interaction with carotenoids and, at thr: same time , a low water solubility which avoids the transfer through the aqueous medi um as well as the matching of the hydrocarbons chains of the carotenoid bet ween lipid bilayer chains, suggesting a relation between drugs structure, b ilayer thickness and membrane interaction. (C) 1999 Elsevier Science B.V. A ll rights reserved.