The present work shows a structural study on the process of incorporation of a hydrophobic drug, Ellipticine (ELPT), into lipid model membranes for drug targeting purpose. The ELPT is an alkaloid that showed an anti-proliferation activity against several types of tumor cells and against the HIV1 virus. We used the zwitterionic lipid dipalmitoyl phosphatidylcholine (DPPC) and four different anionic lipids: cardiolipin (CL), dipalmitoyl phosphatidic acid (DPPA), dipalmitoyl phosphatidylglycerol (DPPG) and dipalmitoyl phosphatidylserine (DPPS), both spread on a Langmuir monolayer and deposited on a solid substrate to mimic a model membrane and study the interaction with the drug ELPT. X-ray reflectivity results pointed toward an increase in drug loading efficiency up to 13.5% mol/mol of ELPT into mixed systems DPPC/CL. This increase in loading efficiency was also accompanied by a slight distortion in the stacking of the bilayers less evidenced after optimization of the molar ratio between the co-lipids. Grazing incidence X-ray diffraction measurements revealed an in-plane lattice distortion due to the presence of hydrocarbon chain backbone ordering in pure systems of DPPC doped with ELPT. The same was not observed in mixed membranes with DPPC/CL and DPPC/DPPA.