Nikita G Yabbarov

Russian Research Center for Molecular Diagnostics and Therapy · Department of Biotechnology

Biocompatible, biodegradable polymers are actively used as drug delivery systems and as tissue engineering scaffolds. The hydrothermal aging of polymers, including degradation of the microstructure and changes of mechanical properties directly depends on environmental conditions. In vitro studies in a model media cannot contain and describe all the...

Photodynamic therapy (PDT) in oncology is characterized by low invasiveness, minimal side effects, and little tissue scarring. Increasing the selectivity of PDT agents toward a cellular target is a new approach intended to improve this method. This study is devoted to the design and synthesis of a new conjugate based on meso-arylporphyrin with a lo...

The effect of the hemin (Hmi) on the structure and properties of nanocomposite electrospun materials based on poly-3-hydroxybutyrate (PHB) is discussed in the article. The additive significantly affected the morphology of fibers allowed to produce more elastic material and provided high antimicrobial activity. The article considers also the impact...

A novel amphiphilic cationic chlorin e6 derivative was investigated as a promising photosensitizer for photodynamic therapy. Two cationic –N(CH3)3+ groups on the periphery of the macrocycle provide additional hydrophilization of the molecule and ensure its electrostatic binding to the mitochondrial membranes and bacterial cell walls. The presence o...

Previous studies have demonstrated the applicability of alpha-fetoprotein or its receptor-binding domain fused to the 6-histidine tag at the C-terminus (rAFP3D-His6) as vectors for targeted delivery of antitumor agents. The His6 tag is undesirable for further preclinical trials. Therefore, we designed a recombinant protein rAFP3D without any affine...

While histone deacetylase inhibitors, such as vorinostat, demonstrate significant effect against hematological cancers, its application for solid tumors treatment is limited. However, there is strong evidence that combinatorial administration of vorinostat and genotoxic agents (e.g., doxorubicin) enhance the antitumoral action of both drugs against...

Currently, molecular dynamics simulation is being widely applied to predict drug-polymer interaction, and to optimize drug delivery systems. Our study describes a combination of in silico and in vitro approaches aimed at improvement in polymer-based nanoparticle design for cancer treatment. We applied the PASS service to predict the biological acti...

Background: Serious side effects caused by paclitaxel formulation, containing toxic solubilizer Cremophor ® EL, and its nonspecific accumulation greatly limit clinical paclitaxel application. Aim: To design paclitaxel-loaded copolymer of lactic and glycolic acids nanoparticles decorated with alpha-fetoprotein third domain (rAFP3d-NP) to increase pa...

Capsules with shells based on nanoparticles of different nature co-assembled at the interface of liquid phases of emulsion are promising carriers of lipophilic drugs. To obtain such capsules, theoretically using the Derjaguin–Landau–Verwey–Overbeek (DLVO) theory and experimentally using dynamic light-scattering (DLS) and transmission electron micro...

Pheophorbide a 17-diethylene glycol ester (XL-8), is a promising high-active derivative of known photosensitizer chlorin e6 used in photodynamic therapy. However, high lipophilicity and poor tumor accumulation limit XL-8 therapeutic application. We developed a novel XL-8 loaded with poly(D,L-lactide-co-glycolide) nanoparticles using the single emul...

Background Difficult to express peptides are usually produced by co-expression with fusion partners. In this case, a significant mass part of the recombinant product falls on the subsequently removed fusion partner. On the other hand, multimerization of peptides is known to improve its proteolytic stability in E. coli due to the inclusion of body f...

Introduction. The use of the anticancer drug paclitaxel is limited due to its high toxicity and lipophilicity. A new polymer composition of paclitaxel has been proposed, which provides targeted transport of the drug into tumor cells and improves its safety. Aim. Method development for preparation of a novel paclitaxel formulation consisting of a co...

The selection of technological parameters for nanoparticle formulation represents a complicated development phase. Therefore, the statistical analysis based on Box–Behnken methodology is widely used to optimize technological processes, including poly(lactic-co-glycolic acid) nanoparticle formulation. In this study, we applied a two-level three-fact...

Previous studies have demonstrated the applicability of alpha-fetoprotein or its receptorbinding domain fused to the 6-histidine tag at the C-terminus (rAFP3D-His6) as vectors for targeted delivery of antitumor agents. This tag is undesirable for further preclinical trials. Therefore, we designed a recombinant protein rAFP3D without any affine tags...

Relevance. A chemotherapeutic agentpaclitaxel (Ptx) has limited usage because of the pronounced side effects of excipients and the non-specificity of Ptx action. We proposed a novel Ptx formulation for targeted therapy of malignant neoplasms and reducing the level of side effects. Aim of the study was to develop a normative documentation for standa...

Mitochondrial dysfunction is known to be associated with a wide range of human pathologies, such as cancer, metabolic, and cardiovascular diseases. One of the possible ways of mitochondrial involvement in the cellular damage is excessive production of reactive oxygen and nitrogen species (ROS and RNS) that cannot be effectively neutralized by exist...

Objectives: The goal of this study was to develop sample preparation method and validate the HPLC method for precise determination of paclitaxel (Ptx) in PLGA submicron particles conjugated with protein vector molecule. Methods: Ptx loaded PLGA submicron particles were formulated by a single emulsification method. PLGA submicron particles were conj...

A UV spectrophotometric method for quantitative determination of paclitaxel in a conjugate of poly(lac-tic-glycolic acid) (PLGA) copolymer nanoparticles and a protein vector (recombinant third domain of alpha -fetoprotein) was developed. Paclitaxel was determined at wavelength 260 ± 2 nm. The proposed method showed specificity, linearity (R 2 = 0.9...

The history of metalloporphyrins dates back more than 200 years ago. Metalloporphyrins are excellent catalysts, capable of forming supramolecular systems, participate in oxygen photosynthesis, transport, and used as contrast agents or superoxide dismutase mimetics. Today, metalloporphyrins represent complexes of conjugated π-electron system and met...

FIELD: medicine. SUBSTANCE: invention relates to an anti-tumour agent which is a ready dosage form in the form of a lyophilizate for parenteral administration for targeted delivery of particlesinto the affected organs and tissues, as well as for prolonged action. Anti-tumour agent contains an alpha-hydroxybenzole propane acid derivative, a lactic a...

New high-molecular-weight contrast agents based on polyamidoamine (PAMAM) dendrimers for targeted imaging of malignant tumors characterized by overexpression of human epidermal growth factor receptor (EGFR) and human alpha-fetoprotein receptor (RECAF) were designed. Conjugates of second (G2) and third (G3) generation polyamidoamine dendrimers with...

Разработаны новые высокомолекулярные контрастные агенты на основе полиамидоаминовых (PAMAM) дендримеров для селективной визуализации злокачественных новообразований, характеризующихся гиперэкспрессией рецептора эпидермального фактора роста (REGF) и рецептора альфа-фетопротеина (RECAF). Получены конъюгаты полиамидоаминовых дендримеров второго (G2) и...

Reactive oxygen species are generated by the redox reaction involving metalloporphyrin and ascorbic acid (AA) and lead to oxidative stress followed by cancer cell death. Polymer particles based on the copolymer of lactic and glycolic acid (PLGA) containing FeIIICl-tetraphenylporphyrin (FeClTPP) were prepared and characterized. These particles in co...

В результате окислительно-восстановительной реакции с участием металлопорфирина и аскорбиновой кислоты (АК) образуются активные формы кислорода, приводящие к окислительному стрессу в опухолевых клетках и последующей их гибели. Получены и охарактеризованы полимерные частицы на основе сополимера молочной и гликолевой кислот (ПМГК), содержащие FeIIICl...

Mitochondrial dysfunction underlies several human chronic pathologies, including cardiovascular disorders, cancers and neurodegenerative diseases. Impaired mitochondrial function associated with oxidative stress can be a result of both nuclear and mitochondrial DNA (mtDNA) mutations. Neurological disorders associated with mtDNA mutations include mi...

The mechanisms of binary catalyst therapy (BCT) and photodynamic therapy (PDT) are based on the formation of reactive oxygen species (ROS). This ROS formation results from specific chemical reactions. In BCT, light exposure does not necessarily initiate ROS formation and BCT application is not limited to regions of tissues that are accessible to il...

Dystonia associated with Huntington's disease, Parkinson's disease or other neurodegenerative diseases substantially affects patients’ quality of life and is a major health problem worldwide. The above‐mentioned diseases are characterized by neurodegeneration accompanied by motor and cognitive impairment and often have complex aetiology. A frequent...

Despite the presence of a variety of modern anticancer drugs at the market, doxorubicin (Dox) is still widely used in antineoplastic therapy, although its administration causes severe side effects. To enhance specific activity of such molecules, various approaches have been exploited: targeted moieties like monoclonal antibodies, onco-specific prot...

Данное пособие содержит информационный материал о методах анализа, позволяющих изучать и проводить характеристику многих наноносителей, в частности, полимерных частиц, и предназначено для студентов химикотехнологических, химико-фармацевтических и фармацевтических вузов и кафедр. Пособие подготовлено на кафедре Биотехнологии и промышленной фармации...

Силибин (Slb) и урсодезоксихолевая кислота (UDCA) — гепатопротекторы, применяющиеся для патогенетической терапии печени и желчевыводящих путей. Однако низкая биодоступность этих препаратов ограничивает их применение. С целью решения данной проблемы проведена работа по включению Slb и UDCA в полимерные носители на основе полимолочной кислоты и сопол...

Silybin (Slb) and ursodeoxycholic acid (UDCA) are hepatoprotectors used in the pathogenetic therapy of liver and biliary tract. However, low bioavailability of these drugs restricts their application. In order to solve this problem, Slb and UDCA were incorporated into polymer carriers based on polylactic acid and poly(lactic-co-glycolic acid) by na...

Co-encapsulation of abiraterone acetate (AbrA) and docetaxel (Dtx) in polymeric nanoparticles as novel prototypes for prostate cancer treatment combining hormonal and chemotherapy was designed. Nanoparticles (NPs) composed of poly(dl-lactide-co-glycolide) (PLGA) were prepared by single-emulsion solvent evaporation technique and characterized in ter...

При использовании метода «двойных эмульсий» разработана технология получения полимерных частиц, содержащих даунорубицин (ДНР), на основе биодеградируемого полилактидгликолида (сополимера молочной и гликолевой кислот, ПМГК) для оптимизации фармакокинетики препарата, повышения уровня его накопления в опухолевой ткани и пролонгации действия. Полученны...

Method for the synthesis of polymeric nanoparticles (NP) with encapsulated daunorubicin (DNR) was developed on the basis of double emulsion solvent evaporation technique using biodegradable poly(lactide-co-glycolide) (PLGA), which is aimed at customization of pharmacokinetic properties of the preparation, enhanced accumulation of DNR in tumor cells...

A wide range of methods are known to increase the prokaryotic intracellular recombinant proteins solubility, for instance, growth at low temperature, supplementation of culture media with “chemical chaperones” (proline, glycine-betaine, and trehalose), co-expression with chaperones or highly soluble fusion partners. As an alternative, we have intro...

In order to study the possibility of using a metal complex of the porphyrin series, FeIIICl-tetraphenylporphyrin (FeClTPP), and its polymeric form as antitumor agents for binary catalytic therapy, the technology of preparation of polymer particles containing FeClTPP was developed for the first time. The experimental data obtained allow one to concl...

С целью изучения возможности применения металлокомплексного соединения порфиринового ряда — FeIIICl-тетрафенилпорфирина (FeClТФП) и его полимерной формы в качестве противоопухолевого средства для проведения бинарной каталитической терапии впервые разработана технология получения полимерных частиц, содержащих FeClТФП. Полученные экспериментальные да...

Purpose: The aim of this study was to compare the physico-chemical and biological properties of polymeric nanoparticles obtained from poly(DL-lactide-co-glycolide) (PLGA) with different ratios of monomers loaded with daunorubicin (DNR). Methods: DNR-loaded nanoparticles (NPs) were prepared with use of modified simultaneous double-emulsion solven...

Anticancer activity of doxorubicin (Dox), its conjugates with the second generation dendritic polymer (G2-Dox) and vector protein (recombinant third domain of alpha-fetopro-tein - 3D-G2-Dox were studied in vitro and in vivo within the framework of the development of selective transport system of anticancer drugs to the target cells. The objects of...

Известно, что опухолевые стволовые клетки (ОСК) представляют собой наиболее радио- и химиорезистентную популяцию в составе широкого ряда злокачественных новообразований, включая рак молочной железы. В связи с этим усилия многих специалистов в области экспериментальной онкологии и радиобиологии направлены в последнее время на разработку средств/спос...

To the article “Antitumor activity of carboplatin in the composition of a copolymer of lactic and glycolic acids,” by E. D. Nikolskaya, O. A. Zhunina, N. G. Yabbarov, V. A. Zenin, O. G. Tereshchenko, M. V. Fomicheva, M. B. Sokol, A. V. Lobanov, and E. S. Severin, Vol. 66, No. 10, pp. 1867–1872, October, 2017. In the original international version o...

Разработаны полимерные частицы, содержащие карбоплатин (CPt), путем включения данного противоопухолевого агента в сополимер молочной и гликолевой кислот (ПМГК-СООН 50/50). Полимерные частицы имеют сферическую форму, их средний диаметр не превышает 200 нм, а величина ζ-потенциала составляет –32.2±1 мВ. Полимерные частицы с CPt обладают цитотоксическ...

Разработана полимерная форма джозамицина путем включения данного антибиотика в частицы сферической формы субмикронного размера из сополимера молочной и гликолевой кислот (ПМГК 50/50). Средний диаметр частиц не превышает 150 нм, а значение дзета-потенциала составляет -35 мВ. Полимерная форма обладает антибактериальной активностью в отношении грампол...

Polymer particles containing carboplatin (CPt) were developed by the inclusion of this antitumor agent in a copolymer of lactic and glycolic acids (PLGA-COOH 50/50). The polymer particles were found to have a spherical form with an average diameter not exceeding 200 nm, the ζ-potential is equal to–32.2±1 mV. The CPt-loaded polymer particles possess...

The dendritic polymers (dendrimers) are perspective nanocontainers for targeted transport of anticancer drugs to tumor cells. We used polyamidoamine dendrimers of the second generation (G2) covalently conjugated with doxorubicin (Dox) and vector protein - recombinant third domain (3D) of alpha-fetoprotein. The objects of the study were MCF-7/MDR1 b...

FIELD: pharmacology. SUBSTANCE: invention is a method of preparing antitumor composition for chemotherapy of oncological diseases and antitumor pharmaceutical composition for chemotherapy of oncological diseases comprising taxol, polylactide-glycolide, bovine albumin and glucose, wherein the components of the composition are at a certain ratio by w...

Группа изобретений относится к области медицины и биотехнологии и может быть использовано для получения противоопухолевых препаратов, содержащих конъюгат на основе альфа-фетопротеина и противоопухолевого средства. Конъюгат характеризуется тем, что получен в виде частиц из сополимеров молочной и гликолевой кислот с включенным в них противоопухолевым...

Temozolomide (TMZ) is a cytostatic drug used in treatment of patients with malignant gliomas and melanomas. The development of innovative formulations for delivery of TMZ into target cells in order to reduce its systemic toxicity and gain prolonged effect is a topical problem of modern biotechnology and phar-macology. The article presents experimen...

Dendritic polymers have a huge potential as a molecular cargoes with targeting abilities in diagnosis and treatment of cancer. The amine-terminated (16 primary amino-groups) and acetyl-terminated (14 primary amino-groups out of 16 were blocked) 2nd generation PAMAM dendrimers (G2 and G2ac respectively) were conjugated with doxorubicin (Dox) and abs...

One of the main directions of modern pharmacology is the target drug delivery to the specific loci of the human body. The advantage of this approach is the ability to reduce the effective dose of the drugs bypassing of passive diffusion and directionally delivery to tumor target cells. Principal for this approach is the creation of chemically or bi...

Темозоломид (TMZ) – цитостатический препарат, обладающий противоопухолевой активностью в отношении злокачественной глиомы и метастазирующей злокачественной меланомы. Создание инновационных способов доставки TMZ в клетки-мишени, обеспечивающих снижение его токсичности и пролонгированный эффект, является актуальной задачей современной биотехнологии и...

A new pharmaceutical form of the antitumor drug docetaxel (Dtx) has been developed based on a biodegradable copolymer of lactic and glycolic acids (PLGA 50/50). This form was constituted of polymeric particles (250 to 300 nm in size) and was highly active against mouse mammary adenocarcinoma (Ca755) and human breast adenocarcinoma (MCF-7 Wt) cell l...

Разработана новая лекарственная форма противоопухолевого препарата доцетаксела (Dtx) на основе биодеградируемого сополимера молочной и гликолевой кислот (PLGA 50/50). Данная форма представляет собой полимерные частицы размером 250–300 нм и обладает высокой активностью в отношении клеток аденокарциномы молочной железы мышей и человека (линии Са755 и...

В дрожжевой системе P. pastoris получен рекомбинантный альфа-фетопротеина (рАФП) и подтверждена его функциональная активность. Разработан способ получения полимерных частиц, содержащих дактиномицин, и осуществлён синтез конъюгата с рАФП на их основе. Была показана эффективность полученного конъюгата в отношении опухолевых клеток линий HeLa, SKOV3 и...

A recombinant alpha-fetoprotein (rAFP) was obtained in the yeast P. pastoris system, and its functional activity was confirmed. A method for producing polymer particles loaded with dactinomycin was developed, and a conjugate of these nanoparticles with rAFP was synthesized. The efficiency of the obtained conjugate on the HeLa, SKOV3, and MG-63 tumo...

Полиамидоаминовые (PAMAM) дендримеры 2-го поколения (G2) представляют собой разветвлен-ные полимеры, содержащие 16 первичных аминогрупп на поверхности, благодаря чему их можно использовать в качестве универсальных носителей при создании систем доставки лекарственных препаратов. Высокий положительный заряд подобных молекул зачастую опосредует их выс...

Second-generation (G2) polyamidoamine (PAMAM) dendrimers are branched polymers containing 16 surface primary amine groups. Due to their structural properties, these polymers can be used as universal carriers in various drug delivery systems. Amine-terminated PAMAM dendrimers are characterized by a high positive surface charge, leading to effective...

Проведено исследование физико-химических свойств биотехнологически полученной фармацевтической субстанции дактиномицина методами ВЭЖХ, ЯМР, МС-спектроскопии и 3D-спектрофлоуриметрии, а также определение биологических свойств дактиномицина в отношении клеток карциномы шейки матки человека лини HeLa. Исследование проводилось путем сравнения свойств с...

The possible acute toxicity and antitumor activity of the novel protein-targeted delivery drug — «Afotid» — was investigated. The biodegradable PLGA nanoparticles were loaded by active cytostatic agent and then conjugated with AFP. Objective. Main research objectives are the precise determination of toxicity levels and study of anti-neoplasctic act...

Accumulation of doxorubicin (Dox), its conjugates with the second generation dendritic polymer (G2-Dox) and vector protein (recombinant third domain of alpha-fetoprotein - 3D-G2-Dox) in normal and tumor cells was studied in vitro within the framework of the development of selective transport system of anticancer drugs to the target cells. The objec...

Polyamideamine (PAMAM) dendrimers have branched structure with terminal primary amine groups. Over the past few years, dendrimers have been used with increasing frequency as carriers for delivery of biologically active compounds into cells and also for the controlled release of drugs, for example, doxorubicin. Several research groups were reported...

The dendritic polymers (dendrimers) are perspective nanocontainers for transportation of anticancer drugs into cells and a controlled release of the delivered substances. However, the combined effect of ionizing radiation and dendrimers loaded with anticancer drugs has been poorly studied and is the aim of this research. We used poliamidoamin (PAMA...

Polyamidoamine (PAMAM) dendrimers of the second generation (G2) are branched polymers containing 16 surface amino groups that allow them to be used as universal carriers on creating systems for drug delivery. G2 labeled with fluorescein isothiocyanate (FITC) efficiently bound with the surface of tumor cells at 4°C and was absorbed by the cells at 3...

The use of vector molecules for the targeted delivery of antitumor drugs provides their selectivity for cancer cells. The recombinant receptor-binding fragment of alpha-fetoprotein (rAFP3D) was used as a vector molecule. The specific receptor of alpha-fetoprotein is a universal tumor marker, being expressed on the surface of many tumor cells, but n...

Biodegradable polymeric nanoparticles conjugated with targeting vector molecules have become prospective agents to improve the effectiveness of chemotherapeutic cancer treatment. This approach reduces the systemic toxicity of the drugs and increases the specificity of their uptake by cancer cells. A method has been developed to obtain complex nanop...