ИСТИНА

Use of spherical monolamellar bilayer lipid vesicles (liposomes) as containers for delivery was suggested after their discovery in the middle of previous century. Due to unique structure, liposomes are used for encapsulation of different substances for improving their physical, chemical and operational characteristics. This makes liposomal containers promising for encapsulation and delivery of various therapeutic, diagnostic and cosmetic agents. Liposomes immobilized on suitable surfaces can act as more capacious depots for pharmaceutical active compounds, and remain stable until they reach the target side. Unfortunately, due to liposome-surface and liposome-liposome interactions, fusion and rupture events are common during adsorption particularly at higher coverage. We suggest to use spherical polycationic brushes – colloidal particles with a condensed core and a shell of grafted linear polycationic chains – as carriers for liposomes. Anionic liposomes effectively adsorb on the cationic brush surface and retain their integrity. This allows one to concentrate dozens of liposomes with entrapped bioactive compounds within a rather small volume. In this work we demonstrate the simple way of preparation of multi-liposomal compositions of vesicles bearing different substances in desired proportions – the key to creation of multi-target drug. A special problem of liposomal containers is to force liposomes to release a content at a target site for enhancing therapeutic effect of drugs. It has been shown that a decrease in pH value (increase of acidity) is typical for pathological physiological pathways, e.g. inflammation, solid tumor progression, ischemic injuries of heart and brain tissues, etc. Thus, the change in pH can serve as an attractive stimulus to trigger a drug delivery system. Incorporation of pH-triggerable lipid (flipid), capable to change conformation with decrease in pH, in membrane of anionic liposomes allowed us to control release of hydrophilic substances from multi-liposomal containers. Stability of liposomes/brush complexes towards dissociation in physiological media, their rather low toxicity and pH-controlled release of encapsulated substances make these structures promising for use as nanocontainers for delivery of biological active compounds. This work was supported by Russian Science Foundation project № 14-13-00255