ИСТИНА

INTRODUCTIONSpherical lipid bilayer vesicles (liposomes) are widely used for delivery of biological active substances. Hydrophilic compounds can be encapsulated into the inner water cavity of liposomes while the hydrophobic can be embedded into the liposomal membrane. We suggest electrostatic assembly of anionic liposomes with the use of polycationic colloid particles for concentration of liposomes within a small volume. This approach allows one to create multiliposomal carriers filledwith different substances at desirable content ratios1. EXPERIMENTALSTUDYSmall unilamellar liposomes, prepared from mixtures of anionic and zwitterionic lipids, were complexed with “spherical polycationic brushes” (SPB), colloidal particles bearing grafted linear cationic macromolecules on their surface and cationic polylactide micelles composed of mixture of amino-terminated lactide and co-polymer of lactide and polyethyleneglycol. To control the complexation and properties of the resulting complexes, the multi-method approach was used including fluorescence spectroscopy, dynamic light scattering, laser microelectrophoresis, cryogenic transmission electron microscopy (cryo-TEM); SAXS, differential scanning calorimetry, conductometry, etc.. RESULTS AND DISCUSSIONThe fraction of anionic lipid (α) in liposomes is the critical factor that affects the aggregation stability of liposome/polyelectrolyte complexes, the reversibility of complexation and the integrity of polymer-bound liposomes. Special attentionhas been paid to structural rearrangements in the liposomal membrane induced by the cationic particles. Interaction of complexes with bovine serum albumin has shown that polymer-liposomes complexes do not decompose in biological medium and retain their nanocontainer properties. Complexation of polycations with liposomes allowed us to obtain structures with cytotoxicity close to toxicity of initial biocompatible liposomal vesicles.The use of polylactide micelles as carriers for the liposomes allowed us to obtain completely biodegradable multiliposomal compositions CONCLUSIONWe have delevoped completely biodegradable multiliposomal nanocontaiers with low cyto-toxicity. The composition and properties of these constuctions could be defined by variation of the liposomal membrane composition and/or choice of polymer carrier.Loading of the series of liposomes with different substances allows us to create with multitask systems with desirable composition. REFERENCES1. A.A. Yaroslavov et. al, Adv. Colloid Int. Sci. 226, 54 (2015) ACKNOWLEDGMENTSThis work was supported by Russian Science Foundation (project 14-13-00255) and byRussian Foundation for Basic Research (projects17-03-00433and 16-03-00375)