Chitosan-based multi-liposomal complexes: Synthesis, biodegradability and cytotoxicity

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. • Liposomes were adsorbed on chitosan particles forming multi-liposomal complexes (MLCs). • MLCs degraded, being attacked by proteolytic enzymes, down to 10–15 nm particles. • The longer chitosan macromolecules, the slower enzyme-induced degradation of MLC. • Variation in pH and cholesterol incorporation had slight effect on biodegradation rate. • MLCs and products of their biodegradation demonstrated low cytotoxicity.