Anionic liposomes were electrostatically adsorbed onto the surface of cationic chitosan particles cross-linked by sulfate anions, forming multi-liposomal containers (MLCs) for encapsulation and delivery of bioactive substances. An increase in molecular mass of chitosan from 30 to 300 kDa results in a size increase of chitosan particles, from 200 to 400 nm. Being saturated by liposomes, chitosan particles give MLCs of 320-540 nm. Each chitosan particle carries between 60 and 200 liposomes. The proteolytic complex Morikrase, a mixture of enzymes with various specificities, induces degradation of MLCs down to particles of size 10-15 nm; the higher the molecular mass of chitosan, the slower the enzyme-induced MLCs' degradation. pH variation within 5.5-7 and cholesterol incorporation into the liposomal membrane both have a minor effect on the rate of MLCs' biodegradation. Both the MLCs and the products of their biodegradation show low cytotoxicity. These results are of interest for constructing biodegradable capacious carriers of bioactive substances. (c) 2021 Elsevier B.V. All rights reserved.

Dendrimers are individual macromolecular compounds having a great potential for biomedical application. The key step of the cell penetration by dendrimers is the interaction with lipid bilayer. Here, the interaction between cationic pyridylphenylene dendrimer of third generation (D350+) and multicomponent liquid (CL/POPC), solid (CL/DPPC) and cholesterol-containing (CL/POPC/30% Chol) anionic liposomes was investigated by dynamic light scattering, fluorescence spectroscopy, conductometry, calorimetric studies and molecular dynamic (MD) simulations. Microelectrophoresis and MD simulations revealed the interaction is electrostatic and reversible with only part of pyridinium groups of dendrimers involved in binding with liposomes. The ability of dendrimer molecules to migrate between liposomes was discovered by the labeling liposomes with Rhodamine B. The phase state of the lipid membrane and the incorporation of cholesterol into the lipid bilayer were found to not affect the mechanism of the dendrimer - liposome complex formation. Rigid dendrimer adsorption on liposomal surface does not induce the formation of significant defects in the lipid membrane pave the way for possible biological application of pyridylphenylene dendrimers.

Complexes of a cationic pyridylphenylene dendrimer with solid and fluid anionic liposomes are prepared. Adsorption of the dendrimer on the surface of liposomes causes the neutralization of their surface charge and enlargement of the dendrimer–liposome aggregates. In interacting with fluid liposomes, the dendrimer does not induce the transition of negatively charged lipid molecules from the inner monolayer into the outer one (flip-flop). The prepared liposome–dendrimer aggregates contain 80 dendrimer molecules per liposome.

The preparation of multiliposomal complexes by adsorption of anionic cholesterol-containing liposomes on the surface of cationic chitosan microparticles has been described. The use of liposomes with a mole fraction of cholesterol in the liposomal membrane of 0.3 forms a complex in which each microparticle binds 150 intact liposomes. The size of complex particles (250–400 nm) allows recommending them as a potential carrier of medicinal substances that can penetrate into the cells through the mechanism of passive transport.