Аннотация:Increasing the efficiency of drug delivery to target cells and organs is a key task of pharmacology. Bilayer lipid vesicles (liposomes) are among the drug carriers that have been intensively used for drug immobilization. pH-sensitive liposomes have great potential for biomedical applications, in particular as nanocontainers for the delivery of biologically active compounds to specific areas of the human body, since lower pH is typical for tumors, areas of inflammation, etc. A great number of pH-sensitive liposomes have been described, but, thereby, it is still a considerable challenge to prepare liposomes that could quickly release the encapsulated substance under small changes in the pH. We suggest the new type of pH-sensitive liposomes with embedded ampholytic molecular switch (AMS) with anionic and cationic groups attached to the opposite ends of the steroid core. The AMS is able to change the orientation in the lipid membrane depending on the acidity/basicity of the external solution, which is accompanied by disordering of the bilayer and rapid release of the encapsulated substance.To increase the therapeutic effect and efficiency of delivery, anionic liposomes are concentrated on the surface of a cationic biodegradable polymer carrier by electrostatic adsorption. This results in multi-liposomal and multi-functional core–shell carriers capable of carrying a mixture of various drugs in the desirable ratio; this is actually a way to design therapeutic agents for treatment of a particular patient. Biodegradable components (polymer and liposomes) ensure the removal of containers from the body after performing the transport function. At the same time, the composition of the lipid membrane has a significant effect on the properties of the complexes formed. The geometry of the lipids forming the membrane, the phase state of the bilayer, and the concentration of charged lipids should be taken into account. To prevent the fusion of liposome membranes, and, accordingly, premature release of the encapsulated substance, as well as to ensure prolonged circulation of the multiliposomal complexes in the bloodstream, the liposomes are modified with a hydrophilic polymer, polyethylene oxide. Liposomes recommended as drug carriers contain cholesterol, which increases the stability of liposomes in the biological environment. Information about the effect of liposome omposition on the structure and properties of multi-liposomal containers is of key importance, as it determines the possible biomedical use of multi-liposomal constructions and can be used to control their properties.
