ИСТИНА

For the first time, the properties of new fliposomes have been investigated by a variety of experimental methods. Fliposomes are a new type of liposomes sensitive to a change of pH due to triggerable lipid-like compound incorporated into those membrane. Fliposomes studied in this report were composed of neutral and anionic lipids and trigger-lipid based on morpholinocyclohexanol. The benefit of pH sensitivity is opportunity to control the process of loading and release from liposomes. Sodium chloride, cesium chloride and carboxifluorescein have been used as the compounds for the model drug loading. Hydrophilic compound release followed by conductometry or fluorimetry could be tuned by pH value of the media. Cesium chloride is a good contrast agent for visualisation of loading in microscopy experiments. Cryo-TEM method was used to visualize the presence and loading properties of fliposomes in solution. It was proven that polydisperse 40-60 nm fliposomes exist in solution. Such fliposomes have different release ratio at different pHs. At low pH values, no cesium chloride was visible inside of fliposome interior, in contrast with neutral pH value, when high contrast cesium chloride was identified inside of liposomes. Small-angle X-ray scattering method additionally prove the existence of fliposomes and their pH sensitivity in solution. The SAXS data at three pH values (3.0, 5.0, and 7.0) were successfully fitted by a three-shell model. From the fitting, the values of experimental scattering length densities (SLDs) for internal compartment and each shell together with their thicknesses were obtained. The SLD value for the intermediate shell is lower than for two outer shells that is in agreement with the vesicular structure of liposomes. Acknowledgements. The financial support of the Russian Foundation for Basic Research (grant No 16-33-01083) is acknowledged.