부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.tsf.2007.11.054 Byline: Agata WiAcek (a), Patrycja Dynarowicz-AAtka (a), J. MiA[+ or -]ones (b), Olga Conde (b), Matilde Casas (b) Keywords: Edelfosine; Cholesterol; Mixed Langmuir monolayers; Air/water interface Abstract: Edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine, abbr. Et-18-OCH.sub.3) is a new generation anticancer drug based on a phospholipids-like structure. Since its mechanism of action is believed to be related to the lipids of cellular membrane, we have investigated the interactions between edelfosine and main mammalian sterol: cholesterol, using the Langmuir monolayer technique. The interactions have been analyzed by comparing the experimental curves with theoretical ones, obtained basing on the additivity rule. The observed contraction together with negative deviations from ideality observed on the mean molecular area (A.sub.12) vs film composition plots proves the existence of strong attractive forces between edelfosine and cholesterol, which have been quantified with the excess free energy of mixing ([DELTA]G.sup.exc) values, calculated from the surface pressure-area isotherms datapoints. The most negative values of [DELTA]G.sup.exc have been found for the mixture of equimolar composition, proving its highest thermodynamic stability and the existence of the strongest interactions between film components. Thus, it has been postulated that at the surface edelfosine and cholesterol form stable complexes of 1:1 stoichiometry. The analysis of the collapse pressure values for the investigated mixed monolayers proves that films of edelfosine mole fraction[less than or equal to]0.5 are miscible within the whole range of surface pressures, while monolayers richer in edelfosine mix in the pressure region below ca. 37.6 mN/m, which corresponds to the collapse of pure edelfosine monolayer. At this very surface pressure, edelfosine is expelled from the mixed monolayer and the remaining film is composed by surface complexes of high stability. The hypothesis of complex formation explains the results performed in vitro on cell cultures, indicating that the increase of cholesterol content significantly reduces the uptake of edelfosine. Author Affiliation: (a) Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060, Krakow, Poland (b) Department of Physical Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, Campus Sur s/n, 15706 Santiago de Compostela, Spain