Elena Nikolskaya

Recently, we have described the first supermolecular nanoentities of vitamin B12 derivative, viz. monocyano form of heptabutyl cobyrinate, unique nanoparticles with strong noncovalent intermolecular interactions, emerging optical and catalytic properties. Their nearest analogue, heptametyl cobyrinate (ACCby), exhibits bioactivity. Here, we demonstr...

Relevance .The aim is evaluation in vitro antiproliferative activity of T. spiralis larvae extracts obtained from experimentally infected rats, depending on the duration of infection. Methods . The experiment was carried out on outbred male rats infected with T. spiralis larvae at the rate of 10 larvae per 1 g of body weight. The antiproliferative...

In this study, we described physico-chemical properties of novel nanoformulation of photosensitizer-pyropheophorbide α 17-diethylene glycol ester (XL) (chlorophyll α derivative), revealing insights into antitumor activity and maintaining quality, meeting the pharmaceutical approach of new nanoformulation design. Our formulation, based on poly(lacti...

The applicability of beam-plasma chemical reactors generating cold hybrid plasma for the production of noncytotoxic polymeric surfaces with high hydrophilicity and good biocompatibility with human fibroblast culture and human red blood cells was studied. Oxygen hybrid plasma was excited by the joint action of a continuous scanning electron beam and...

Unsaturated fatty acids, such as oleic acid (OA) and linoleic acid (LA), are promising antimicrobial and cytostatic agents. We modified OA and LA with thymol (TOA and TLA, respectively) to expand their bioavailability, stability, and possible applications, and encapsulated these derivatives in polymeric nanoparticles (TOA-NPs and TLA-NPs, respectiv...

The combination of two or more medications is increasingly more common in the development of new treatment guidelines for common diseases. Thus, the use of combinations of histone deacetylase inhibitors with chemotherapeutic agents is a current trend in solid tumor treatment. The aim of this study was to investigate an effective vorinostat (SAHA) t...

Metal–organic Frameworks (MOFs) are widely used in the biomedical industry. In this study, we developed a new method for obtaining a metal-organic structure of strontium and terephthalic acid, Sr(BDC), and...

The calcium-carbonate-induced mineralization of multilayer shells of emulsion capsules, formed using layer-by-layer assembly of polyelectrolytes, has been investigated. Optimal conditions for forming microcapsules with a core from shea butter and an organic–inorganic shell from synthetic polyelectrolytes and calcium carbonate are found. The shell m...

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...

The conventional targeted delivery of chemotherapeutic and diagnostic agents utilizing nanocarriers is a promising approach for cancer theranostics. Unfortunately, this approach often faces hindered tumor access that decreases the therapeutic index and limits the further clinical translation of a developing drug. Here, we demonstrated a strategy of...

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...

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...

The paper describes the expression, purification and isolation of native sequence human alpha-fetoprotein recombinant receptor-binding domain and evaluation its functional activity for specific targeting to tumor cells.

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...

Разработан метод количественного определения паклитаксела в составе конъюгата наночастиц на основе сополимера молочной и гликолевой кислот и белковой векторной молекулы (рекомбинантным третьим доменом альфа-фетопротеина) с помощью УФ-спектрометрии. Определение паклитаксела проводили при длине волны (260 ± 2) нм. Доказаны специфичность, линейность (...

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...

The production technology for nanoparticles based on a copolymer of lactic and glycolic acids (PLGA) containing dipropoxybacteriopurpurinimide (DPBPI) and intended for photodynamic therapy of malignant neoplasms of various etiology is optimized. An approach to reducing the average diameter of the resulting nanoparticles is proposed. The obtained DP...

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...

Описан процесс оптимизации технологии получения наночастиц на основе сополимера молочной и гликолевой кислот (PLGA), содержащих дипропоксибактериопурпуринимид (DPBPI) и предназначенных для фотодинамической терапии злокачественных новообразований различного генеза. Предложен подход к снижению среднего диаметра получаемых наночастиц. Получен образец...

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...

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...

The article describes the process of developing a technology for producing nanoparticles based on a copolymer of lactic and glycolic acids (PLGA) containing dipropoxybacteriopurpurinimide (DPBPI) for photodynamic therapy of malignant tumors of various origins. Technological parameters for optimizing the method in order to obtain nanoparticles with...

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...

Изучены закономерности накопления наночастиц на основе сополимера поли-D,L-лактид-ко-гликолида и полиэтиленгликоля в опухолевых клетках человека. Для этого получены и охарактеризованы полимерные наночастицы (ФПН), меченные флуоресцеинизотиоцианатом. Уровень их накопления внутри клеток определяли после «гашения» флуоресценции адсорбированных на пове...

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...

The purpose of this review is to analyze literature data about methods and approaches currently used to create new photosensitizer delivery systems, and to evaluate the effectiveness of their use in anti-cancer photodynamic therapy.

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...

To investigate the patterns of uptake of PLGA-PEG nanoparticles by human cancer cells, FITC-labeled polymer nanoparticles (FPN) are prepared and their properties are characterized. The amount of internalized FPN is measured by flow cytometry after quenching the fluorescence of the membrane-bound nanoparticles with Trypan Blue. The total uptake of t...

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...