Abstract:
The work is devoted to the development of effective and safe biocompatible means and methods of encapsulation, targeted delivery and controlled release of drugs in aqueous environments, including living systems. For encapsulation of medicinal compounds in colloidal carriers, originally created nanostructured biomimetic lipid membrane vesicles were used - nanocomposite liposomes, the membranes of which are functionalized with magnetite and gold nanoparticles. To solve the problem of safe controlled release of an encapsulated substance into aqueous media, an approach has been developed based on the use of powerful ultrashort electrical pulses with a duration of less than 10 ns, providing a non-thermal effect of selective controlled electroporation of nanocomposite lipid membranes containing conductive nanoparticles. A theoretical model of non-thermal interaction of nanostructured liposomal capsules with ultrashort electrical pulses has been developed, within the framework of which an expression has been obtained for the critical value of the electric field strength that determines the threshold for the occurrence of the electroporation effect in a conducting aqueous medium. The key role of electrically conductive nanoparticles in increasing the sensitivity of the structure and conductivity of nanocomposite liposomes to external ultrashort electric sunlight is shown. The theoretically described mechanism of change in the structure and conductivity of lipid membranes containing electrically conductive nanoparticles explains the selective controlled nature of ultrashort pulse action on nanocomposite liposomal containers. The effect of controlled selective change in permeability and decapsulation of nanocomposite liposomes was registered by fluorimetry methods in experiments with the anticancer antibiotic doxorubicin and the fluorescent dye carboxyfluorescein, which were loaded into liposomal carriers as model molecular compounds. Encapsulated substances were released from nanocomposite liposomes after exposure to ultrashort electrical pulses with an efficiency of up to 98%, while no significant changes in the structural and functional state of natural and pure lipid membranes were recorded. The data on changes in membrane permeability correlated well with the results on structural changes in nanocomposite liposomes recorded by transmission electron microscopy and atomic force microscopy.
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