<b>Abstract</b>— <p>Studies of structure and permeability changes of biological and biomimetic lipid membranes caused by natural and artificial factors are currently an important field of fundamental science and applied research. A prominent interdisciplinary area of such research with high potential of biomedical applications is the development of new effective methods of drug therapy aimed at solving the problem of controlled addressed delivery of drugs and genes directly to target areas and cells of the body (spatial-temporal coupling and control of drug delivery). Our 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 media including living systems. For capsulation of drug compounds in colloid carriers we use originally fabricated nanostructured biomimetic lipid membrane vesicles (nanocomposite liposomes) whose membranes are functionalized with magnetite and gold nanoparticles. To solve the problem of safe controlled release of a capsulated drug in the aqueous media we develop an approach based on the use of strong ultrashort electrical pulses with duration of less than 10 ns, providing the non-thermal effect of selective controlled electroporation of nanocomposite lipid membranes containing conductive nanoparticles polarized in applied external electric field. A theoretical model of non-thermal interaction of nanostructured liposomal capsules with ultrashort external electrical pulses has been developed, within the framework of which an expression has been obtained for the critical value of the applied electric field strength, which determines the threshold for the occurrence of the electroporation and decapsulation 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 electrical action 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. Experimentally, the effect of controlled selective changes of permeability and decapsulation of nanocomposite liposomes in our work was recorded by conductometry methods in experiments with liposomes containing a concentrated NaCl solution inside, as well as by fluorimetry methods in experiments with the anticancer antibiotic doxorubicin and fluorescent dye carboxyfluorescein, which were loaded into liposomal carriers as model molecular compounds. Encapsulated payload was released from nanocomposite liposomes after the influence of short strong electric pulses with efficiency up to 98%. The data on membrane permeability changes correlated well with results on structural changes of nanocomposite liposomes registered by transmission electron microscopy (TEM) and atomic force microscopy (AFM) techniques. Obtained experimental data and theoretical estimations demonstrate selective activation and controlled increase in the permeability of nanocomposite lipid membranes in comparison with control liposomes resulting in effective release of encapsulated compounds selectively from nanocomposite lipid vesicles because of external pulsed electrical action without substantial changes of structural-functional state of natural and pure lipid membranes. Selectivity of external control actions only on drug carriers is fundamentally important and necessary for safe control of drug delivery and release in target areas of the body. Our findings open possibilities for development of technological platform for advanced spatial-temporal controlled drug therapy based on functionalized biocompatible biomimetic colloid lipid membrane drug carriers and efficient safe control effects of ultrashort electrical pulses.</p>