ABSTRACT
Gene and synthetic drug-delivery vectors have been developed and characterized to treat several genetic diseases and cancers. Our study aims at characterizing cationic liposomes containing the zwitterionic phospholipid DMPC and the cationic lipid DOTAP as well as their interactions with two types of DNA and a new class of antineoplastic agents derived from arylchloroethylureas (CEU). Results obtained using FTIR spectroscopy as well as (31)P and (2)H NMR indicate that DMPC and DOTAP form cationic liposomes in a highly disordered fluid phase at a molar ratio of 1:1. In addition, the FTIR results indicate that the presence of DNA or CEUs within the liposomes does not significantly affect the conformational order of both the DMPC and DOTAP acyl chains. Our results therefore provide a detailed characterization of complexes between cationic liposomes and both DNA and drugs and indicate that these complexes are stable and fluid assemblies.
Subject(s)
DNA/metabolism , Dimyristoylphosphatidylcholine/chemistry , Fatty Acids, Monounsaturated/chemistry , Liposomes/chemistry , Liposomes/metabolism , Phenylurea Compounds/metabolism , Quaternary Ammonium Compounds/chemistry , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/metabolism , Cations/chemistry , Cattle , DNA/chemistry , Dimyristoylphosphatidylcholine/metabolism , Drug Carriers/chemistry , Drug Carriers/metabolism , Fatty Acids, Monounsaturated/metabolism , Nuclear Magnetic Resonance, Biomolecular , Phenylurea Compounds/chemistry , Plasmids , Quaternary Ammonium Compounds/metabolism , Spectroscopy, Fourier Transform Infrared , Temperature , Thymus Gland/chemistryABSTRACT
We have investigated the interaction between a new class of antineoplastic agents derived from arylchloroethylureas (CEU) with three different model membranes by (31)P and (2)H solid-state NMR spectroscopy. First, we have prepared model membranes that mimic the mitochondrial inner (Mito IM) and outer (Mito OM) membranes and the endoplasmic reticulum membrane (End Ret). Our results indicate that the effects of the CEU derivatives on lipid bilayers are related to their cytotoxic activity. More specifically, a strong correlation is observed between the drug location in both the mitochondrial inner and outer membranes and its cytotoxicity. In addition, the results indicate that the lipid composition of the model membrane has a very important influence on the effects of CEUs. More specifically, a high proportion of cardiolipin in the mitochondrial inner membrane gives this system the highest fluidity and consequently, this model membrane is more rigidified by the presence of CEUs compared to the mitochondrial outer and endoplasmic reticulum membranes. Finally, the results propound a hypothesis for the location of CEUs in membranes.
