This study aims to develop dual-responsive delivery systems based on microgel-liposome complexes, capable of controlled and stepwise cargo release in response to distinct physiological stimuli. Stable multiliposomal complexes were constructed by electrostatic adsorption of small anionic liposomes onto large cationic microgels composed of PNIPAM-co-DADMAC. Two types of liposomes were used: conventional anionic liposomes and pH-sensitive ones incorporating an ampholytic molecular switch. Their release behavior was examined under thermal and pH stimuli. It was shown that the two liposome types responded independently to their respective stimuli: conventional liposomes were disrupted upon microgel collapse above the VPTT (similar to 32 degrees C), whereas switch-containing liposomes remained intact under heating but released their cargo upon acidification. The presence of the molecular switch was found to enhance the mechanical stability of the membrane, allowing selective response. Importantly, cytotoxicity assays confirmed that all components-microgels, liposomes, and their complexes-were non-toxic at relevant concentrations. These findings demonstrate that the developed complexes enable two-stage, stimulus-specific release and highlight the potential of microgel-liposome complexes as advanced platforms for smart drug delivery.

Last decades, we have seen a growing interest in thermonuclear fusion. There are a lot of installation prototypes created for controlled thermonuclear fusion. Our group developing software for numerical simulation of plasma physics processes in an open magnetic trap, which can be used for controlled thermonuclear fusion. This code is Fortran-based code. Parallel implementation using MPI for parallel computations. This parallel implementation is optimized for using CPUs with advanced vectorization instructions such as AVX2/AVX512. In this paper, we will show some optimization techniques for maximizing the performance of our parallel Particle-in-Cell (PIC) code using data alignment. This feature helps the compiler to optimize data and cycles in code during the compilation and building of the program. Also, we will show the performance comparison between optimized and nonoptimized programs and the effect of vector instructions utilization on the total code performance.

A new method of the design of stimuli-sensitive multiliposomal containers for encapsulation and controlled drug release is described. Despite quite a wide choice of pH-sensitive containers, there is still a considerable challenge to synthesize those that respond quickly to small variations in pH and release most of the encapsulated drug in a short time. The suggested AMS-containing multiliposomal complexes demonstrated an excellent rate of encapsulated substance release under altering the pH of the outer solution. To improve the efficiency of the delivery of bioactive compounds to target cells and to increase the therapeutic effect, pH-sensitive liposomes were concentrated on the surface of the carrier- PEG-coated cationic liposomes. A pH-sensitive ampholytic derivative of cholan-24-oic acid embedded into the membrane of anionic liposomes allowed the rapid release of the cargo in the areas of low pH, such as tumors, inflammation sites, etc. The diameter of the complexes was optimized for passive targeting and typically ranged from 250 to 400 nm. The biodegradability of liposomes ensured enzymatic destruction of the multiliposomal containers and their elimination from the body after performing their transport function. The multiliposomal complexes and products of their biodegradation demonstrated low cytotoxicity. The composition of multiliposomal complexes, in particular, the amount of PEGylated lipid in the bilayer, was estimated to provide a high speed of the cargo release upon changing the pH. The novel developed pH-sensitive containers show potential for biomedical applications.

Multiliposomal nanocontainers were obtained by electrostatic adsorption of anionic liposomes on the surface of the carrier- PEG-coated cationic liposomes. The composition of liposomes was estimated, that lead to the formation of multiliposomal complexes of the 200–400 nm size with preserved integrity of the lipid bilayer. The degradation of the complexes under the action of lipase was followed by a quantitative release of incapsulated substance. The complexes seem to be promising for biomedical applications.

Composite films containing poly(vinyl alcohol) filled with different amounts of graphene oxide (2 and 4 wt

Small anionic liposomes were electrostatically adsorbed on the surface of larger cationic liposomes thus forming multi- compartment complexes composed exclusively of natural and synthetic lipids. The complexes contained two dozen anionic liposomes per a single cationic liposome and showed low cytotoxicity and ability to enzyme-induced bio-degradation. The liposomal multi-compartment complexes demonstrate great application potential as containers for drug encapsulation and delivery.

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. In this article, we discuss the possible mechanism of fast cargo release from a new type of pH-sensitive liposomes with embedded ampholytic molecular switch (AMS, 3-(isobutylamino)cholan-24-oic acid) with carboxylic anionic groups and isobutylamino cationic ones attached to the opposite ends of the steroid core. AMS-containing liposomes demonstrated the rapid release of the encapsulated substance when altering the pH of an outer solution, but the exact mechanism of the switch action has not yet been accurately determined. Here, we report on the details of fast cargo release based on the data obtained using ATR-FTIR spectroscopy as well as atomistic molecular modeling. The findings of this study are relevant to the potential application of AMS-containing pH-sensitive liposomes for drug delivery.

The development of new efficient methods for combating serious diseases, among which, oncological and infectious diseases hold a special place, remains to be an urgent challenge of biomedicine and biotechnology. Currently, the efforts of scientists are focused on the search for drug systems that provide high efficiency of treatment with minimal impacts on a human body. The development of this field has led to the creation of stimuli-responsive liposomes that can release an encapsulated drug under a specific stimulus, such as temperature, pH, electromagnetic field, light, etc. Being stimulated, lipid bilayer vesicles change their structure, size, surface charge, or phase state, thus leading to a controlled release of the drug in a specific place of the body, thereby resulting in a more accurate and efficient delivery. This review discusses the current trends in the development of liposome-based stimuli-responsive systems for the controlled delivery of biologically active substances.

In the last decades, dendrimers have received attention in biomedicine that requires detailed study on the mechanism of their interaction with cell membranes. In this article, we report on the role of dendrimer structure in their interaction with liposomes. Here, the interactions between cationic pyridylphenylene dendrimers of the first, second, and third generations with mixed or completely charged pyridyl periphery (D16+, D215+, D229+, and D350+) with cholesterol-containing (CL/Chol/DOPC) anionic liposomes were investigated by microelectrophoresis, dynamic light scattering, fluorescence spectroscopy, and conductometry. It was found that the architecture of the dendrimer, namely the generation, the amount of charged pyridynium groups, the hydrophobic phenylene units, and the rigidity of the spatial structure, determined the special features of the dendrimer–liposome interactions. The binding of D350+ and D229+ with almost fully charged peripheries to liposomes was due to electrostatic forces: the dendrimer molecules could be removed from the liposomal surfaces by NaCl addition. D350+ and D229+ did not display a disruptive effect toward membranes, did not penetrate into the hydrophobic lipid bilayer, and were able to migrate between liposomes. For D215+, a dendrimer with a mixed periphery, hydrophobic interactions of phenylene units with the hydrocarbon tails of lipids were observed, along with electrostatic complexation with liposomes. As a result, defects were formed in the bilayer, which led to irreversible interactions with lipid membranes wherein there was no migration of D215+ between liposomes. A first-generation dendrimer, D16+, which was characterized by small size, a high degree of hydrophobicity, and a rigid structure, when interacting with liposomes caused significant destruction of liposomal membranes. Evidently, this interaction was irreversible: the addition of salt did not lead to the dissociation of the complex.

Aqueous dispersions of mixtures of low-viscosity polyanionic cellulose with microbarite are studied by viscometry, rotational rheometry, dynamic light scattering, and laser microelectrophoresis. Owing to the interaction of the polymer with microbarite particles, the hydrodynamic size of the particles and their electrophoretic mobility increase, which indicates the formation of polymer-colloidal complexes. In the mode of semidilute polymer solutions, the introduction of microbarite additives is accompanied by a significant increase in viscosity and the resulting compositions are sedimentation stable for 2 days. The frequency dependences of the storage modulus and the loss modulus show that complexation leads to a strong structuring of the system.

Reversibility of structural rearrangements in a liquid liposomal membrane upon electrostatic adsorption/desorption of the cationic polymer (chitosan) has been studied. The polycation can be completely removed from the lipid membrane via addition of an excess of polyacrylic acid forming more stable electrostatic complex with chitosan. Removal of chitosan has resulted in complete recovery of the original lipid distributions in lateral and transmembrane directions as well as intervesicular lipid exchange.

Interaction of the cationic polymer chitosan with anionic liposomes has been studied. The characteristics of the polycation-liposome complex have been determined by the phase state of the lipid membrane. Chitosan adsorbed on the surface of liquid liposomes has induced transmembrane migration of anionic lipid from the inner to the outer leaflet. Liquid liposomes have retained their integrity in the complex with chitosan. The adsorbed polymer can be completely removed from the membrane by the addition of a low-molecular electrolyte. The chitosan adsorption on the surface of solid liposomes has led to the formation of defects in the membrane: in this case the polycation adsorption has been irreversible. The established phenomena may be important for the understanding of biological effects of chitosan.

The article proposes a new method for solving the equations of motion of charged particles in electromagnetic fields. In the algorithm, the velocity of a charged particle at a time step is computed in accordance with the exact solution of the differential equation. The method has been compared with various known modifications of the Boris method. The comparison was carried out both in terms of the accuracy of the methods and the time of their operation. A new modification of the method uses the fact that the electric and magnetic fields are constant at a time step. It allows one to compute more accurately the trajectory and velocity of a charged particle without significant increasing the complexity of the computations. It has been shown that when choosing a modification of the Boris method to solve a problem, one should pay attention first of all to the accuracy of the solution, since a simpler and faster scheme may not give a gain in time.

Anionic liposomes were electrostatically adsorbed onto the surface of cationic chitosan particles cross-linked by sulfate anions, forming multi-liposomal containers (MLCs) for encapsulation and delivery of bioactive substances. An increase in molecular mass of chitosan from 30 to 300 kDa results in a size increase of chitosan particles, from 200 to 400 nm. Being saturated by liposomes, chitosan particles give MLCs of 320-540 nm. Each chitosan particle carries between 60 and 200 liposomes. The proteolytic complex Morikrase, a mixture of enzymes with various specificities, induces degradation of MLCs down to particles of size 10-15 nm; the higher the molecular mass of chitosan, the slower the enzyme-induced MLCs' degradation. pH variation within 5.5-7 and cholesterol incorporation into the liposomal membrane both have a minor effect on the rate of MLCs' biodegradation. Both the MLCs and the products of their biodegradation show low cytotoxicity. These results are of interest for constructing biodegradable capacious carriers of bioactive substances. (c) 2021 Elsevier B.V. All rights reserved.

Dendrimers are individual macromolecular compounds having a great potential for biomedical application. The key step of the cell penetration by dendrimers is the interaction with lipid bilayer. Here, the interaction between cationic pyridylphenylene dendrimer of third generation (D350+) and multicomponent liquid (CL/POPC), solid (CL/DPPC) and cholesterol-containing (CL/POPC/30% Chol) anionic liposomes was investigated by dynamic light scattering, fluorescence spectroscopy, conductometry, calorimetric studies and molecular dynamic (MD) simulations. Microelectrophoresis and MD simulations revealed the interaction is electrostatic and reversible with only part of pyridinium groups of dendrimers involved in binding with liposomes. The ability of dendrimer molecules to migrate between liposomes was discovered by the labeling liposomes with Rhodamine B. The phase state of the lipid membrane and the incorporation of cholesterol into the lipid bilayer were found to not affect the mechanism of the dendrimer - liposome complex formation. Rigid dendrimer adsorption on liposomal surface does not induce the formation of significant defects in the lipid membrane pave the way for possible biological application of pyridylphenylene dendrimers.

Stimulus-sensitive liposomes have been prepared from zwitterionic dioleoylphosphocholine and ampholytic molecular switches with carboxylic anionic groups and the triazole or isobutylamino cationic ones attached to the opposite ends of the steroid core. When the pH of outer solution was altered from slightly alkaline to slightly acidic, the switches changed their orientation in the liposomal membrane, which induced temporal defects formation and the release of a drug model load. The low-toxic pH-sensitive isobutylamino derivative–dioleoylphosphocholine liposomes demonstrated fast cargo release.

Positively charged linear chitosan molecules were cross-linked with sulfate-anions to form chitosan nano-particles which were used as a scaffold of negatively charged cardiolipin/egg lecithin liposomes loaded with doxorubicin (DOX). Thus formed multi-liposomal complexes (MLCs) containing 55 liposomes/chitosan and bearing a slight positive net charge effectively transmitted DOX into the cytoplasm of cells in culture. The efficiency of DOX delivery increased 4-5-fold upon drug incorporation in MLCs. Inside the cells, the penetrated MLCs released DOX thus enabling its accumulation in the nuclei and interaction with its intracellular target DNA leading to a decrease in cell survival. The effects were demonstrated on 3T3 line of mouse fibroblasts, drug sensitive tumor MCF-7 cells and drug resistant human ovarian carcinoma OVCAR-8 cells (formerly called MCF-7/ADR). Thus, MLC particles can be used for effective delivery of payloads in cells of different origin.

Nanoparticles of ionically cross-linked chitosan have been prepared from the linear polymer with weight-average molecular mass Mw of 30000, 63000, or 300000 and the molar content of primary amino groups of 0.85. Multi-liposomal complexes have been obtained via electrostatic adsorption of anionic liposomes on the surface of cationic chitosan particles. The effect of the chitosan molecular weight on the size of the final complexes and their stability in a water–salt media have been studied. The conditions for the formation of multi-liposomal complexes with size in the range of 250–450 nm have been determined. We have proposed to use linear chitosan with Mw of 30000 and 63000 to obtain multi-liposomal complexes. The size of the resulting constructions allows them to enter cells via the passive transport mechanism through enlarged pores in blood capillaries in inflammatory foci and tumors.

Synthetic water-soluble polymers are increasingly used for gene delivery, stabilization, and delivery of proteins, and as prospective antimicrobial and antiviral agents. Therefore, study of their interaction with lipid membranes is of special importance. Herein, we studied interaction of aliphatic cationic ionenes (recently tested for gene delivery efficiency) differed in the length of spacer between charged groups (and therefore in charge density) with anionic lipid membrane. A range of approaches such as measurement of particle size and electrophoretic mobility, liposome integrity, ATR-FTIR spectroscopy, isothermal titration calorimetry as well as atomistic molecular modeling was used. Ionene with a spacer of 10 methylene groups has been shown to be incorporated into membrane and interact with its inner hydrophobic part in contrast to ionenes with shorter spacer, which interacted only with outer polar head groups of lipids staying at the water-membrane interface. It affects membrane integrity and results in a different behavior of the polymer-liposome complexes. These findings are relevant for potential biomedical application of ionenes, including creation of composite polymer-liposome systems for drug delivery.

Complexes of a cationic pyridylphenylene dendrimer with solid and fluid anionic liposomes are prepared. Adsorption of the dendrimer on the surface of liposomes causes the neutralization of their surface charge and enlargement of the dendrimer–liposome aggregates. In interacting with fluid liposomes, the dendrimer does not induce the transition of negatively charged lipid molecules from the inner monolayer into the outer one (flip-flop). The prepared liposome–dendrimer aggregates contain 80 dendrimer molecules per liposome.