Various RNAs are among the most promising and actively developed therapeutic agents for the treatment of tumors, infectious diseases and a number of other pathologies associated with the dysfunction of specific genes. Some nanocarriers are used for the effective delivery of RNAs to target cells, including liposomes based on cationic and/or ionizable amphiphiles. Cationic amphiphiles contain a protonated amino group and exist as salts in an aqueous environment. Ionizable amphiphiles are a new generation of cationic lipids that exhibit reduced toxicity and immunogenicity and undergo ionization only in the acidic environment of the cell. In this work we developed a scheme for the preparation and carried out the synthesis of new cationic and ionizable amphiphiles based on natural amino acids (L-glutamic acid, glycine, β-alanine, and γ-aminobutyric acid). Cationic and ionizable liposomes were formed based on the obtained compounds, mixed with natural lipids (phosphatidylcholine and cholesterol), and their physicochemical characteristics (particle size, zeta potential, and storage stability) were determined. Average diameter of particles stable for 5–7 days did not exceed 100 nm. Zeta potential of cationic and ionizable liposomes was about 30 and 1 mV, respectively. The liposomal particles were used to form complexes with RNA molecules. Such RNA complexes were characterized by atomic force microscopy and their applicability for nucleic acid transport was determined.

The Gag polyprotein is the major structural protein of the human immunodeficiency virus (HIV). It is responsible for the assembly of new viral particles in the infected cell. This process takes place at the plasma membrane of the cell, and is largely regulated by the interactions of Gag with the lipid matrix of the cell membrane. In this work, we used the inner field compensation method and electrokinetic measurements of the zeta potential in a liposome suspension to study the binding of the non-myristoylated HIV Gag polyprotein to model lipid membranes. To quantify the affinity of the protein for charged and uncharged lipid bilayers, Gag adsorption isotherms were constructed and binding constants were calculated. It was shown that the protein is able to interact with both types of membranes with approximately the same intrinsic binding constants (KPC = 8 × 106 M–1 and KPS = 3 × 106 M–1). However, the presence of the anionic lipid phosphatidylserine in the lipid bilayer significantly enhances protein adsorption onto the membrane ( K_PS^eff = 37.2 × 106 M–1), because phosphatidylserine creates a surface potential jump near the membrane. Thus, the interaction of Gag with membranes is determined more by hydrophobic interactions and the area per lipid molecule, while the presence of a negative surface charge only increases the concentration of the positively charged protein near the membrane.

Mitochondria are the “power stations” of cells. Without them, the normal functioning of a living cell is impossible. This organelle is an attractive target for antitumor therapy because of the variety of processes in which mitochondria are involved and the differences between mitochondria in healthy and tumor cells. In this review, various approaches to the development of diagnostic and therapeutic agents selectively directed to the mitochondria of tumor cells are described. The main mitochondrial vector ligands are described, as well as their conjugation with known antitumor drugs and combination with common drug delivery systems.

This work is aimed to develop several cationic amphiphiles based on amino acid derivatives of diethanolamine as potentially membrane-active antibacterial agents. The developed compounds contain two amino acid residues in the polar block and aliphatic chains of various length in the hydrophobic domain. Amphiphiles were obtained in preparative amounts sufficient to confirm their structures and perform a study of antibacterial activity. The synthesized samples based on β-Ala (4c) and GABA (4d) with aliphatic C12 chain in the hydrophobic domain showed a promising level of antimicrobial activity against gram-positive (B. subtilis) and gram-negative (E. coli) bacteria (minimal inhibitory concentration, MIC, 1 μg/mL). Amphiphiles containing aromatic amino acids L-Phe (6a) and L-Trp (6b) in the polar head group and C8 hydrocarbon chain exhibited an antibacterial activity against B. subtilis with MIC of 1 μg/mL. The obtained data on antimicrobial activity make the selected compounds attractive for further detailed study of their mechanism of action.

This work aimed to produce mixed liposomes based on natural amino acids as vehicles for delivery of anticancer drugs and nucleic acids. Liposomes were formed from cationic lipids based on L-alanine and L-serine, a cerasome-forming lipid based on L-ornithine, and phospholipids phosphatidylcholine (PC) or 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). For the developed agents, particle size, zeta potential, and stability were determined, and the biological activity was studied on the MCF-7 and HEK 293 cell lines. Liposomes based on L-serine demonstrated the ability to accumulate in the endoplasmic reticulum of cells within 1 h, and their transfection activity significantly exceeded that of the commercial drug Lipofectamine-2000. At the same time, the proposed system had a slight toxic effect (IC50, 0.475 mg/mL and the safe working concentration, 0.24 mg/mL). Thus, the results suggest that mixed liposomes based on L-serine can serve as an efficient delivery system of drugs into cells.

Objectives. Resistance to antibiotics and other antimicrobial drugs is an acute problem in the world today. Therefore, the chemical and pharmaceutical industries are still in search of new antibacterial agents that can overcome the resistance of pathogenic bacterial strains. To date, it has been established that molecules with antimicrobial activity must have an amphiphilic nature, a small size, one or more positive charges, and the required degree of hydrophobicity, that is, a significant hydrophilic–lipophilic balance (HLB) value. Some examples of such structures are antimicrobial peptides or peptidomimetics. This study aimed to develop a universal scheme for synthesizing several amino acid derivatives based on diethanolamine diesters with symmetric and asymmetric radicals in a hydrophobic block and potential antibacterial activity.Methods. The progression of chemical reactions was analyzed using thin-layer chromatography (TLC) on Sorbfil plates. The obtained compounds were isolated and purified using preparative TLC on Kieselgel (Merck) 60 F254 plates and column chromatography on Merck silica gel 0.040–0.063 mm. The TLC method was used to detect substances using a 3% ninhydrin solution, followed by heating to 70 °C. The structures of the obtained compounds were confirmed by hydrogen-1 nuclear magnetic resonance (1H NMR) spectroscopy on a Bruker WM-300 pulse NMR spectrometer, with hexamethyldisiloxane serving as the internal standard.Results. The HLB values of the diethanolamine derivatives were calculated, and samples were selected for subsequent synthesis. A scheme was developed for preparing amino acid derivatives based on diethanolamine diesters with symmetric and asymmetric radicals in the hydrophobic domain, and five new compounds were synthesized. The hydrophilic blocks of these compounds included residues of amino acids such as glycine, β-alanine, L-ornithine, and L-lysine.Conclusions. The potential antimicrobial activity of the synthesized peptidomimetics was assessed by their HLB values using the ACD/Labs Log P program. New amphiphiles were synthesized using amino acids and diethanolamine, and their structures were confirmed by 1H NMR spectroscopy data. The synthesized compounds were prepared for antibacterial activity analysis.

This study is aimed at creating a number of derivatives of natural amino acids based on dioctylamine and diethanolamine diesters with potential antibacterial activity. Simple and universal schemes of the synthesis allow them to be used for obtaining a series of samples in the preparative quantities necessary for the implementation of physiochemical and biochemical studies. The synthesized sample based on glycyldioctylamide shows a promising level of antimicrobial activity (MIC) against Gram-positive and Gram-negative bacteria.

— Modern pharmaceutics aims at creating new drugs with high bioavailability, biocompatibility and efficiency, as well as minimally toxic effects. One of the ways to reach this goal is to create nanosized particles that carry a small but sufficient dose of a medicinal drug. The diversity of nanoscale delivery systems allows designing therapeutic complexes with necessary characteristics. Liposomes are lipid vesicles with a bilayer membrane possessing the properties required for transportation of various drugs and genes. They consist of natural components, which can minimize cytotoxicity. In addition, the creation of artificial cationic lipids makes it possible to adjust the properties of delivery systems to particular purposes. Cerasomes are organosilicon particles that have been developed to overcome the low stability of liposomes. These are nanoscale spherical aggregates consisting, like liposomes, of a lipid bilayer, but their surface is modified by a silicone polymer network. Cerasomes have all advantages of liposomes. This review presents basic methods for the synthesis of liposome components and cerasome-forming lipids to create stable delivery systems. Different variants of cationic lipid structures and modifications of cerasome-forming lipids are presented. Potential areas of their application are described, including gene transfection, photodynamic therapy, visualization and diagnosis of diseases using magnetic resonance, and tumor treatment.

Nowadays, chemotherapy is an important mean for cancer treatment. Despite many benefits, patients receiving anticancer drugs often suffer unfavorable side effects due to the non-specific toxicity of anticancer drugs. Most anticancer drugs can kill cancer cells with non-selective killing of the normal human cells, which brings great pains to patients. One of the most important tasks facing pharmacology is the creation of such systems that would minimize the harm caused by therapeutic drugs. One way to overcome these problems is to create drug delivery systems. Much attention is attracted the liposomes as delivery systems. They consist of natural components that can minimize toxicity in relation to the human body, so liposomes are interest to study. However, one of the limitations preventing the wide use of liposomes is their insufficient stability under physiological conditions. This property can lead to the fact that the drug will be released from the delivery system until the desired cells or tissues are reached, which means that it damages healthy cells. The problem of stability can be solved by systems called cerasomes. These are nanosized spherical particles consisting of the lipid bilayer as well as liposomes, but their surface is modified by a silicon polymer network. Liposomal nanohybrid cerasomes have been developed based on organoal-koxysilane through a sol-gel reaction in combination with self-assembly process. Among inorganic materials, silicon is an excellent choice to form hydrophilic surface shell due to its high chemical resistance, optical transparency and low physiological toxicity. In addition, cerasomes have better biocompatibility than silicon nanoparticles that have a similar size. They are inert and exhibit less cytotoxicity. Cerasomes are very convenient to store for a certain time due to their physical and chemical properties. Equally important is the fact that cerasomes are capable of encapsulate a wide range of drug molecules. Water-soluble drugs are built into the internal field of the vesicles, and hydrophobic drugs are built into the bilayer lipid membrane. So cerasomes can solve many problems associated with drug molecules like low drug solubility, fast clearance rates, non-specific toxicity, thereby enhancing therapeutic efficiency and reducing side effects. Also, various functional molecules can be included to cerasomes that show thermo-, light-, pH- or multi sensitive properties by chemical conjugation with different molecules in order to modulate the release behavior of the drug. Therefore, cerasomes, serving as delivery carriers, possess great potential for clinical applications due to their unique advantages. This review will summarize the progress of liposomal nanohybrid cerasomes and their applications as drug nanocarriers, transfection of gene materials, systems for visualization and diagnosis of diseases using MRI and PDT. It presents some methods of the synthesis of cerasome-forming lipids to create stable systems of cerasomes. Various approaches of the formation of a siloxane network on their surface are considered. Various variants of modifications of cerasome-forming lipids are presented.

Research methods based on the use of RNA interference mechanisms are now included among the basic methods of molecular biology. Drugs based on siRNA are being developed for the treatment of cancer, infectious diseases and other pathologies that are associated with impaired Junctions of specific genes. One of the main problems of siRNA-based drug development is their efficient and safe delivery to target cells. Modern delivery strategies are based on the use of chemical compounds or biological carriers, such as viruses. Lipid nanoparticles (liposomal agents) are the most advanced platform among non-viral vectors for the delivery of gene materials into cells. In this paper, a scheme has been proposed and the synthesis of new cationic amphiphiles has been carried out as the basis for the means of delivering siRNA to target cells. Synthesized amphiphiles belong to two types of cationic lipids: with a permanently charged amino group in the form of a salt and with an ionizable polar block. Ionized amphiphiles are a new generation of cationic lipids that exhibit reduced toxicity and immunogenicity. They undergo ionization only in the acidic environment of endosomes during intracellular transport in the cytosol, which leads to the release of the encapsulated cargo. The structure of the target compounds is based on diethanolamine derivatives, which is a spacer between the hydrophobic block and the polar fragment. The hydrophobic block contains palmitoyl residues, and the polar one - ethylenediamine and 3-diethylaminopropylamine derivatives. The developed synthetic scheme is distinguished by the simplicity and versatility of the proposed approach, which allows it to be used in the preparation of a series of samples in preparative quantities necessary for the subsequent physicochemical and biochemical studies.

The paper describes the production of a number of lipoamino acid derivatives based on L-serine, L-ornithine, and L-lysine with potential antibacterial activity. The designed synthesis schemes are distinguished by the simplicity and versatility of the approach used. This allows us to use them to obtain a series of samples in preparative quantities required to perform the subsequent physico-chemical and biochemical studies.