Liposomal formulations of antitumor drugs. II. effect of lipid compositions on membrane interactions of europium coordination complexes

摘要

Currently there is a growing interest in screening of new drugs, capable of destroying cancer cells effectively, without damaging health tissues. In this context the potential of liposomes as a drug carrier system is extensively investigated [1-3]. Liposomes are nanosize particles in which lipid bilayer encloses an aqueous internal compartment. Size, charge and surface properties of liposomes can be easily changed simply by adding new ingredients to the lipid mixture before liposome preparation or by variation of preparation techniques. Another important feature is that lipid vesicles can entrap both hydrophilic and hydrophobic pharmaceutical agents. Liposome delivery systems can enhance drug solubility, reduce toxicity associated with free anticancer drugs and improve stability of the drug by protecting the compound from chemical degradation or transformation. However, the therapeutic and toxic effects of drug are strongly determined by the degree or efficiency of its loading into the liposomes. For this reason, while using liposomes as delivery systems for hydrophobic drugs, it is necessary to know the character of a drug effect on the structure and physicochemical properties of a lipid bilayer. The aim of this work was to investigate the effect of lipid composition on membrane interactions of europium coordination complexes, V3 and V4, the potential antineoplastic drugs. Liposomes were formed by egg yolk phosphatidylcholine (PC) and its mixture with cardiolipin (CL) and cetyltrimethylammonium bromide (CTAB). The membrane-partitioning properties of the investigated drugs were evaluated using the equilibrium dialysis technique in combination with absorption spectroscopy. To gain insight into the drug influence on physical parameters and molecular organization of lipid bilayer, two fluorescent probes have been employed, viz. pyrene and 1,6-diphenyl-1,3,5-hexatriene (DPH). It was found that inclusion of anionic lipid cardiolipin and cationic detergent CTAB into PC bilayer gives rise to decrease of the drugs partition coefficients. The drug incorporation into liposomal membrane is accompanied by the alterations of pyrene spectral parameters and DPH anisotropy. The observed effects suggest that the influence of europium compounds on bilayer structural state can be modulated by CL and CTAB.