Study of the correlation between the structure of selected triester of phosphatidylcholine and their impact on physicochemical properties of model mammalian membranes

Abstract

Cationic lipids are synthetic compounds of amphiphilic character used in Drug Delivery Systems (DDS), especially in gene therapy, as the carriers of genetic material. As it is known, the main limitation of the application of cationic lipids in DDS is their high cytotoxicity after in vivo administration and low bioactivity. This is probably related to not fully known the relationship between the lipid structure and its activity as well as the mechanism of lipofection or drug delivery. Therefore, in this work we determined the impact of a selected group of cationic lipids - triesters of phosphatidylcholine (Et-PCs) - differing in their hydrophobic structure on model mammalian membranes. In the research, as model systems, Langmuir monolayers and liposomes were applied. It was shown that the incorporation of Et-PCs into model mammalian membranes weakens interactions between lipids, causing the increase of fluidity, disordering degree and permeability of membrane. The destabilization of the membrane in this way can facilitate the entry of drugs, carried inside cationic liposomes, into the pathological cell. Moreover, the studies prove that the structure of the hydrophobic part of cationic lipids also affects the properties of lipid membranes.