Complexes of anionic liposomes and a cationic polymer: Composition, structure, and characteristics

Adsorption of the synthetic polycation poly-N-ethyl-4-vinylpyridinium bromide (PEP) on the surface of bilayered lipid vesicles (liposomes) is studied. Two types of liposomes are used: (i) traditional two-component liposomes formed from neutral phosphatidylcholine (PC) and anionic diphosphatidylglycerol (cardiolipin, CL2−) and (ii) PC/CL2− anionic liposomes with the built-in nonionogenic surfactant poly(ethyleneglycol) cetyl ether with a degree of polymerization of 20 (Brij-58). PEP is quantitatively linked with both types of liposomes; this process is electrostatic in character and fully reversible. The formation of a poly(ethylene glycol) layer on liposomal membrane decreases the stability of polycation-liposome complexes in aqueous salt solutions. Adsorption of PEP on the surface of PC/CL2− liposomes is accompanied by their aggregation; PC/CL2−/Brij liposomes do not aggregates, even during complete neutralization of their charge by the adsorbed PEP. DSC measurements showed that the adsorption of the polycation is accompanied by microphase separation in the liposomal membrane: formation of domains, which are composed primarily of CL2− molecules and linked to the complex with PEP, and regions, where electroneutral lipids are primarily concentrated. With the use of a spin probe, the packing density of bilayers (their microviscosity) is estimated, and a preferential localization of the probe at the boundaries of lipid domains in the membrane based on PC/CL2−/Brij liposomes is proposed. The causes of the aggregative stability of three-component PC/CL2−/Brij liposomes are described, and the structure of the prepared polymer-liposome complexes is discussed.