Interactions of dimethoxycurcumin (1) a lipophilic bioactive curcumin derivative with dipalmitoyl phosphatidylcholine (DPPC) were investigated. The thermodynamic changes caused by (1) and its location into DPPC lipid bilayers were monitored by differential scanning calorimetry and Raman spectroscopy. The results reveal that (1) influences the thermotropic properties of DPPC lipid membrane causing abolition of the pretransition and broadening of the phase-transition profile and slightly decreases the T. at increasing concentrations. The Raman height intensify ratios of the peaks I-2935/2880, I-2844/2880 and I-1090/1130 are representative of the interaction of (1) with the alkyl chains and furnish information about the ratio between disorder and order that exists in the conformation of the alkyl chain. The intensity changes of the peak at 715 cm(-1) indicates interaction between the choline head group and (1). The Raman spectroscopy results are in agreement with the thermal analysis results. Biologically active lipophilic molecules such as (1) should be studied in terms of their interaction with lipid bilayers prior to the development of advanced lipid carrier systems such as liposomes. The results of these studies provide information on the membrane integrity and physicochemical properties that are essential for the rational design lipidic drug delivery systems. (C) 2006 Elsevier B.V. All rights reserved.