Vol 9, No 1 (2021)

Dendrimers are nanoparticles with unique features including globular 3D shape and nanometer size. The availability of numerous terminal functional groups and modifiable surface engineering permit modification of dendrimer surface with several therapeutic agents, diagnostic moieties and targeting substances.

The aim. To enlighten the readers regarding design, development, limitations, challenges and future directions regarding anticancer bio-dendrimers.

Materials and methods. The data base was represented by such systems as Medline, Cochrane Central Register of Controlled Trials, Scopus, Web of Science Core Collection, PubMed. gov, Google-Academy. A search was carried out for the following keywords and combinations: Polypropylene imine (PPI); Poly-L-lysine (PLL); Polyamidoamine (PAMAM); cancer; drug delivery; dendrimers.

Results. High encapsulation of drug and effective passive targeting are also among their therapeutic uses. Herein, we have described latest developments in chemotherapeutic delivery of drugs by dendrimers. For the most part, the potential and efficacy of dendrimers are anticipated to have considerable progressive effect on drug targeting and delivery.

Conclusion. The newest discoveries have shown that the dendritic nanocarriers have many unique features that endorse more research and development.

The aim of the review is to provide an analysis and generalization of the main directions of research in the sphere of pharmaceutical services, and their characteristics associated with the determination of their main development trends.

Materials and methods. For the analysis, the information store on the basis of scientific publications by Russian and foreign scientists, devoted to research in the field of pharmaceutical services (PSs), has been used. The search for publications was carried out in the open and accessible sources of the latest twenty years (the retrospective period of 2001–2021), located in scientific and technical libraries of institutions, as well as in electronic databases: Elibrary, Medline / PubMed, Cochrane Library, Scopus, CyberLeninka, Google-Academy, J-stage. When forming the information array, the search for publications was carried out according to the following requests: pharmaceutical services (pharmaceutical care services), the provision of pharmaceutical services, the quality of pharmaceutical services. For the conceptualization of the study, 87 scientific publications obtained as a result of information retrieval, have been used.

Results. In the course of the study, a logical and structural analysis of the main directions in which research in the field of providing PSs in our country is developing, has been carried out. The main trends in the study of the providing services’ activity in the sphere of drug circulation, are characterized. A comprehensive analysis of the category of “pharmaceutical service” has been carried out. The terminological content of this concept, the groups of features characterizing the economic and social essence of educational institutions have been generalized, and the most characteristic features that make up the structure and content of educational institutions, have been identified. The existing approaches to the development of the nomenclature and types of PSs have been analyzed and the systematization of pharmaceutical works and services using the process approach, have been proposed by the authors.

Conclusion. The conducted study indicates the presence of several directions in the development of research in the field of providing PSs, aimed at improving the quality of services for the population in pharmaceutical organizations. However, the most important role in the research is assigned to the study and assessment of the quality of educational institutions, the development of approaches to its optimization. As evidenced by the results of the analysis and generalization, the most successful activity in the provision of services in the field of drug circulation requires the implementation of a process approach and the implementation of Quality Management Systems (QMSs).

The aim of this study is to develop a universal, rapid and affordable method for the identification of dydrogesterone, troxerutin, and ademetionine in drugs by multisensor digital colorimetry using a unique two-dimensional code. The developed approach can be applied to rapid detection of counterfeit drugs at the preliminary stage of the analysis (before using more expensive specialized equipment).

Materials and methods. To implement the proposed approach, the substances of dydrogesterone (“Abbott Biologicals B.V.”, Netherlands), troxerutin (JSC “Interfarma”, Prague, Czech Republic) and ademetionine (LLC “Farmamed”, Moscow, Russia), troxerutin capsules 300 mg (LLC “Pranafarm”, Samara, Russia), lyophilisate for an intravenous solution and the intramuscular administration “Heptral”^® (ademetionine) 400 mg (“Abbott Laboratories”, GMBH, Germany), tablets “Duphaston”^® (dydrogesterone) 10 mg (“Abbott Healthcare Products B.V.”, Netherlands), were used. A multisensor colorimetry method has been implemented using the following set of 8 sensors (C₁–C₈): an intact solution – a 96% (v/v) aqueous ethanol solution – C₁; 1 mM alcoholic solution of anthraquinone green (CAS#4403-90-1) – C₂; a 0.2% aqueous solution of 3-methylbenzothiazolinone hydrazone (CAS#1128-67-2) – C₃; a 0.2% methyl orange aqueous solution (CAS#547-58-0) – C₄; a 1 mM alcoholic solution of sulforhodamine B (CAS#3520-42-1) – C₅; a 1 mM alcoholic solution of 1-hydroxypyrene (CAS#5315-79-7) – C₆; 1 mM alcoholic solution of allura red AC (CAS#25956-17-6) – C₇; a 1 mM aqueous solution of iron (III) chloride – C₈. Transparent flat-bottomed polypropylene plates with 96 cells, with a cell volume of 350 µl (Thermo Fischer Scientific, USA, cat. No. 430341) were used as a base for the chip. For obtaining raster images, an Epson Perfection 1670 office flatbed scanner (CCD-matrix) with a removable cover was used. The obtained digital images of the cells were processed using the ImageJ software (Wayne Rasband, National Institutes of Health, USA; http://imagej.nih.gov/ij) with a 24-bit RGB color model (8 bits per channel).

Results. The adequacy of the developed approach was confirmed by the analysis of the above-listed drugs. It has been shown that the results obtained have no statistically significant differences from the values determined by the spectrophotometric method.

Conclusion. The possibility of using multisensor digital colorimetry for pharmaceutical analysis has been shown. The developed methods for the identification of the active substances can serve as a good supplement to more expensive traditional methods.

The first of the most successfully implemented nootropic drugs in medical practice is piracetam, which should be attributed to cyclic derivatives of gamma-aminobutyric acid. The production of new piracetam derivatives with high nootropic activity is a promising direction in the development of new neuroprotective drugs.

The aim of the study is to predict GABA-ergic and glutamatergic activities of N-acyl derivatives of 2-(2-oxopyrolidin-1-yl)-acetamide by a molecular docking method through the energy analysis of interaction of modeled structures with GABA_A and AMPA receptors with their subsequent targeted synthesis.

Materials and methods. The objects of the research are new N-acyl derivatives of 2-oxo-1-pyrrolidineacetamide and a virtual model of the GABA_A receptor of the Homo sapiens organism with the identification code 6D6U and a three-dimensional model of the AMPA-receptor of the Rattus norvegicus organism with the identification code 3LSF from the RCSB PDB database. The simulated compounds were designed in the HyperChem 8.0.8 program. This program was also used to optimize geometry using the force field of molecular mechanics MM+. Molecular docking was carried out using the Molegro Virtual Docker 6.0.1 program. The preparation of N-acyl derivatives of 2-(2-oxopyrrolidin-1-yl)-acetamide was carried out by the interaction of 2-(2-oxopyrrolidin-1-yl)-acetamide with an excess of the corresponding anhydride under conditions of acid catalysis.

Results. Based on the results of molecular docking, a high affinity of all simulated compounds for the binding site of GABA_A and AMPA receptors can be estimated. According to the predict, the maximum GABA-ergic activity should be expected for (N-[2-(2-oxopyrrolidin-1-yl)-acetyl]-butyramide. N-acyl derivatives of 2-oxo-1-pyrrolidineacetamide form a more stable complex with amino acid residues Arg207, Phe200, Thr202, Tyr97, Tyr157, Tyr205 and Phe65 of the GABA_A receptor binding site than the GABA molecule. In terms of the minimum interaction energy, the N-acyl derivatives of 2-(2-oxopyrrolidin-1-yl)-acetamide are superior to a number of known ligands such as GABA, piracetam, anipiracetam, picamilon and pramiracetam. The tested compounds have also shown a high affinity for the binding site of the AMPA receptor. The leader compound is also the compound PirBut, as in the case of the GABA_А receptor.

Conclusion. Molecular modeling of the ligands interaction with the active binding site of gamma-aminobutyric acid of the GABA_A receptor by molecular docking showed that all virtual N-acyl derivatives of 2-oxo-1-pyrrolidineacetamide can exceed a number of nootropic drugs by activity. In the course of molecular design, a method for predicting a glutamatergic activity for 2-pyrrolidone derivatives has been developed. It suggests a significant nootropic activity for N-[2-(2-oxopyrrolidin-1-yl)-acetamide amides.