title: pH dependence of daunorubicin interactions with model DMPC:Cholesterol membranes.
abstract: Mixed monolayers composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC):Cholesterol 7:3 prepared by the Langmuir-Blodgett method were used as model membranes to investigate the influence of the anticancer drug daunorubicin (DNR) on the properties of the lipid membrane. The Langmuir monolayer experiments revealed that drug - membrane interactions are pH-dependent. The changes in monolayer organization at subphases of pH 7.4 containing daunorubicin visualized by Brewster Angle Microscopy showed that in the presence of the drug the typical morphology observed for phospholipid layers containing cholesterol was no longer seen. It supports the explanation of the mechanism of the drug incorporation into the layers in terms of the competition between DNR molecules and cholesterol in the layer. Increasing surface pressure with time and increasing value of limiting surface pressure with increasing drug concentration in the subphase confirmed incorporation of the drug into the membranes. The interactions between the lipid monolayer and the drug at pH 5.4 were of electrostatic nature between the negative part of the DMPC molecule and positively charged drug, while at pH 7.4 contribution of interactions of daunorubicin with cholesterol was observed. Large differences of the surface-pressure vs. time plots were observed at both pH values when the DMPC:Cholesterol monolayer was not well organized yet. The voltammograms recorded for DMPC:Cholesterol monolayers transferred from the air-water interface onto gold electrode confirmed the presence of the drug in the lipid layer. Based on the charge of the oxidation-reduction peaks corresponding to the redox processes of quinone-hydroquinone group in daunorubicin, the initial surface concentration of the drug in the membrane and the drug release profile to the solution were evaluated.
authors.affiliation: Biological and Chemical Research Centre, University of Warsaw, Żwirki i Wigury 101, 02-089 Warsaw, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Matyszewska
authors.affiliation: Faculty of Chemistry, University of Warsaw, ul. Pasteura 1, 02093 Warsaw, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Brzezińska
authors.affiliation: Biological and Chemical Research Centre, University of Warsaw, Żwirki i Wigury 101, 02-089 Warsaw, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Juhaniewicz
authors.affiliation: Faculty of Chemistry, University of Warsaw, ul. Pasteura 1, 02093 Warsaw, Poland. Electronic address: bilewicz@chem.uw.edu.pl.
authors.forename: Renata
authors.initials: R
authors.lastname: Bilewicz
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000737:chemistry*; D002784:Cholesterol / Q000737:chemistry*; D003630:Daunorubicin / Q000737:chemistry*; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008567:Membranes, Artificial; D008956:Models, Chemical; D013499:Surface Properties
chemical_list: D000903:Antibiotics, Antineoplastic; D008567:Membranes, Artificial; D002784:Cholesterol; D004134:Dimyristoylphosphatidylcholine; D003630:Daunorubicin
keywords: 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC); Brewster angle microscopy (BAM); Cholesterol (Chol); Cyclic voltammetry; Daunorubicin (DNR); Langmuir monolayer; model lipid membrane