Elena Markvicheva

• Russian Academy of Sciences

Hydrogels from natural polysaccharides are of great interest for tissue engineering. This study aims (1) to prepare hydroxyapatite‐loaded macroporous calcium alginate hydrogels by novel one‐step technique using internal gelation in water‐frozen solutions; (2) to evaluate their physicochemical properties; (3) to estimate their ability to support cel...

Silk fibroin (SF) holds promise for the preparation of matrices for tissue engineering and regenerative medicine or for the development of drug delivery systems. Regenerated fibroin from Bombyx mori cocoons is water-soluble and can be processed into scaffolds of various forms, such as fibrous matrices, using the electrospinning method. In the curre...

Silk fibroin (SF) extracted from Bombyx mori cocoons is a biocompatible and biodegradable polymer shows potential as matrices for tissue engineering and regenerative medicine, or con-trolled drug delivery systems. Regenerated fibroin, obtained by removing sericin from natural silk, is water-soluble. Its aqueous solutions can be processed into a var...

The objectives of the study were as follows: (1) to develop two methods for the preparation of macroporous composite chitosan/hyaluronic acid (Ch/HA) hydrogels based on covalently cross-linked Ch and low molecular weight (Mw) HA (5 and 30 kDa); (2) to investigate some properties (swelling and in vitro degradation) and structures of the hydrogels; (...

Citation: Gileva, A.; Trushina, D.; Yagolovich, A.; Gasparian, M.; Kurbanova, L.; Smirnov, I.; Burov, S.; Markvicheva, E. Doxorubicin-Loaded Polyelectrolyte Multilayer Capsules Abstract: Recently, biodegradable polyelectrolyte multilayer capsules (PMC) have been proposed for anticancer drug delivery. In many cases, microencapsulation allows to conc...

The aim of the study was to fabricate and characterize composite macroporous hydrogels based on a hyaluronic acid/chitosan (Hyal/Ch) polyelectrolyte complex (PEC) loaded with homogeneously distributed hydroxyapatite nanoparticles (nHAp), and to evaluate them in vitro using mouse fibroblasts (L929), osteoblast-like cells (HOS) and human mesenchymal...

Self-assembled nanoparticles based on amphiphilic poly(N-vinylpyrrolidone) (Amph-PVP) were proposed earlier as a new drug delivery system. In the current work, we study the antitumor activity of Amph-PVP-based self-assembled polymeric micelles covalently conjugated with the antitumor receptor-specific TRAIL variant DR5-B (P-DR5-B). The Amph-PVP pol...

Nanoparticles based on the biocompatible amphiphilic poly(N-vinylpyrrolidone) (Amph-PVP) derivatives are promising for drug delivery. Amph-PVPs self-aggregate in aqueous solutions with the formation of micellar nanoscaled structures. Amph-PVP nanoparticles are able to immobilize therapeutic molecules under mild conditions. As is well known, many ef...

Presently, most of anticancer drugs are high toxic for normal cells and, and as a result, they have severe side effects. Moreover, most of the formulations are lipophilic and have poor selectivity. To overcome these limitations, various drug delivery systems could be proposed. The aim of the current study was to fabricate novel polysaccharide nanoc...

Glioblastoma (GBM) is an aggressive and lethal form of brain cancer with a high invasion capacity and a lack of effective chemotherapeutics. Retinoid bexarotene (BXR) inhibits the neurospheroidal colony formation and migration of primary glioblastoma cells but has side effects. To enhance the BXR glioblastoma selectivity and cytotoxicity, we chemic...

Introduction Targeted multimodal approaches need to be strategically developed to control tumour growth and prevent metastatic burden successfully. Breast cancer presents a unique clinical problem because of the variety of cellular subtypes that arise. The tumour stage and cellular subtypes often dictate the appropriate clinical treatment regimen....

Self-stabilizing biodegradable microcarriers were produced via an oil/water solvent evaporation technique using amphiphilic chitosan-g-polyester copolymers as a core material in oil phase without the addition of any emulsifier in aqueous phase. The total yield of the copolymer-based microparticles reached up to 79 wt. %, which is comparable to a yi...

Objectives: The aim of the current study was to develop biodegradable alginate (ALG)/poly-L-lysine (PLL) microcapsules (MC) with entrapped plasmids expressing Gn and Gc glycoproteins of Rift Valley Fever virus (RVFV) and to evaluate the humoral immune response in mice. Results: Expressing phRVF/Gn and phRVF/Gc plasmids which encode full-sized Gn...

Introduction Core fucosylation of N-glycans on the integrin β1 subunit is essential for the functional activity of the integrin. The binding of α5β1 integrin with the tripeptide Arg-Gly-Asp (RGD) motif within the extracellular matrix protein fibronectin may be influenced by the α-1,6-fucose core or α-1,2-fucose and α-1,3/4-fucose peripheral N-glyca...

Introduction. Cutaneous melanoma is a challenge to treat due to rapid progression of disease and acquired resistance to therapy. Autophagy and the epithelial-to-mesenchymal transition (EMT) are closely interrelated and play a key role in tumor progression. Targeted co-inhibition of MEK and mTOR kinases is a potential target for melanoma therapy by...

Doxorubicin (DOX) is one of mainstays in anticancer therapy due to its universal anticancer activity. Development of DOX delivery systems is of particular importance aiming a reduction in its non-targeted toxicity and improvement of the treatment efficiency. In this study, biodegradable polyelectrolyte multilayer capsules from a dextran sulfate (DS...

Melanoma is one of the most aggressive and treatment-resistant tumors that responsible for majority of skin-cancer related deaths. Here we propose a combination of MEK inhibitor binimetinib with metformin as a promising therapy against human melanoma cells in vitro, including BRAF -mutated A375, Mel Z, and Mel IL cells, and NRAS-mutated Mel MTP and...

The monograph consists of reviews prepared by specialists having scientific publications, theoretical knowledge and practical experience in research of immobilized cells of different microorganisms, plants and animals, which they conducted for the last decade. The basis of the reviews is composed by the scientific results of the authors and relevan...

INTRODUCTION Doxorubicin (DOX) is the one of the main stays ofoncologic treatment with a broad spectrum ofantitumor activity. As the other anthracyclines, DOXdemonstrates cardiotoxicity, which is related to thetotal cumulative dose of the drug to which the patienthas been exposed. Therefore the development of DOXdelivery systems is of particular im...

The influence of the conditions of the formation of genipin cross-linked chitosan cryostructurates on the porous morphology and physicochemical properties of these cryostructurates and on the possibility of their use as biopolymer 3D scaffolds for tissue engineering was studied. The chitosan cryostructurates were obtained by freeze-drying a chitosa...

Engineering of a "smart" drug delivery system to specifically target tumour cells has been at the forefront of cancer research, having been engineered for safer, more efficient and effective use of chemotherapy for the treatment of cancer. However, selective targeting and choosing the right cancer surface biomarker are critical for a targeted treat...

Polymer-based containers became very promising carriers proposed for drug delivery, during the last decades especially nanoscale systems are in demand. The aim of the research is to develop polymer capsules using combination of layer-by-layer shell assembly and its subsequent thermo-induced shrinking, and to study their interaction with tumor cells...

The proceedings of 9th International Conference Biomaterials and Nanobiomaterials: Recent Advances Safety-Toxicology and Ecology Issues, 6-13 May, 2018 Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease which is characterized by inflammation and severe damage of various tissues. Phosphorylated P140 peptide, an analogue of small nuc...

Development of efficient biodegradable, environmentally responsive, biocompatible and non-toxic delivery system is needed for efficient gene delivery. As well known, properties of the vehicle are determined by the structure of carrier components. The aim of the current study was to estimate in vitro transfection efficacy of aliphatic di-, tri- and...

Purpose: Multidrug resistance (MDR) of tumors to chemotherapeutics often leads to failure of cancer treatment. The aim of the study was to prepare novel MDR-overcoming chemotherapeutics based on doxorubicin (DOX) derivatives and to evaluate their efficacy in 2D and 3D in vitro models. Methods: To overcome MDR, we synthesized five DOX derivatives, a...

The proceedings of 8th International Conference “Biomaterials and Nanobiomaterials: Recent Advances Safety-Toxicology and Ecology Issues“, 7-14 May 2017

Background Prostaspheres-based three dimensional (3D) culture models have provided insight into prostate cancer (PCa) biology, highlighting the importance of cell–cell interactions and the extracellular matrix (EMC) in the tumor microenvironment. Although these 3D classical spheroid platforms provide a significant advance over 2D models mimicking i...

Chitosan-based hydrogels are considered as promising biomaterials for tissue engineering. Biological properties of chitosan could be significantly improved by modification of its chemical structure. This study was aimed at characterizing macroporous hydrogels fabricated by freeze-drying technique from chitosan, which has been N-acetylated by 2,2-bi...

Objectives: To design novel 3D in vitro co-culture models based on the RGD-peptide-induced cell self-assembly technique. Results: Multicellular spheroids from M-3 murine melanoma cells and L-929 murine fibroblasts were obtained directly from monolayer culture by addition of culture medium containing cyclic RGD-peptide. To reach reproducible arch...

Multicellular tumor spheroids (MTS) have been at the forefront of cancer research, designed to mimic tumor-like developmental patterns in vitro. Tumor growth in vivo is highly influenced by aberrant cell surface-specific sialoglycan structures on glycoproteins. Aberrant sialoglycan patterns that facilitate MTS formation are not well defined. Matrix...

The influence of the conditions of the formation of chitosan hydrogels crosslinked with glutaraldehyde (GA) or genipin (the polysaccharide molecular weight, pH level, and concentration of the chitosan solution) on the gel time and the properties of biopolymer scaffolds for tissue engineering obtained by the freeze-drying of hydrogels was studied. T...

Development of novel anticancer formulations is a priority challenge in biomedicine. However, in vitro models based on monolayer cultures (2D) which are currently used for cytotoxicity tests leave much to be desired. More and more attention is focusing on 3D in vitro systems which can better mimic solid tumors. The aim of the study was to develop a...

Purpose: This study aimed to investigate the impact of the size of X-ray iodinated contrast agent in nano-emulsions, on their toxicity and fate in vivo. Methods: A new compound, triiodobenzoate cholecalciferol, was synthetized, formulated as nano-emulsions, and followed after i.v. administration in mice by X-ray imaging (micro computed tomograph...

Amphiphilic chitosan-g-poly(d,l-lactide) copolymers have been manufactured via solid-state mechanochemical copolymerization and tailored to design polyester-based microspheres for tissue engineering. A single-step solid-state reactive blending (SSRB) using low-temperature co-extrusion has been used to prepare these copolymers. These materials have...

Chitosan-g-oligo (L, D-lactide) copolymers were synthesized and assessed to fabricate a number of 3D scaffolds using a variety of technologies such as oil/water emulsion evaporation technique, freeze-drying and two-photon photopolymerization. Solid-state copolymerization method allowed us to graft up to 160 wt-% of oligolactide onto chitosan backbo...

High toxicity, poor selectivity, severe side effects are major drawbacks of anticancer drugs. Various drug delivery systems could be proposed to overcome these limitations. The aim of the study was to fabricate polysaccharide microcontainers (MC) loaded with thymoquinone (TQ) by one-step ultrasonication technique and to study their cellular uptake...

In the study, MCF-7 human breast adenocarcinoma cells were used to study cytotoxicity of novel anticancer nanosized formulations, such as docetaxel-loaded nanoemulsion and liposomal formulation of a lipophilic methotrexate (MTX) prodrug. In Vitro study of cytotoxicity was carried out in 2 models, namely using 3D In Vitro model based on multicellula...

Microcarriers have been proposed in tissue engineering, namely for bone, cartilage, skin, vascular, central nervous system. Although polyester-based microcarriers have been already used for this purpose, their surface properties should be improved to provide better cell growth. The goal of this study was to prepare microbeads based on poly(D,L-lact...

Surface plasma treatment of chitosan films is a widely used technique to control a variety of their properties, such as permeability, hemostatic activity and ability to support cell adhesion, proliferation and growth. Among other factors to be controlled, the chemical structure of initial chitosan is rarely taken into consideration. This work is ai...

Nanofibrous material was prepared by needle-free electrospinning from a mixture of chitosan and polyvinyl alcohol of equal masses. The conditions for converting it to an insoluble form by heat treatment were studied. The effectiveness of using chitosan-containing nanofibrous material for absorption of uranyl ions from processing solutions and the p...

The work was aimed to study an effect of direct current discharge on chemical structure, surface properties and cell response to the plasma modified composite films. The film samples were prepared by solvent casting from colloidal solution of the ternary blend of chitosan, gelatin and poly(L,L-lactide), PLLA, obtained by solid-state reactive blendi...

The aim of this study was to entrap delta-sleep inducing peptide (DSIP) in cross-linked poly(vinyl alcohol)-based hydrogels of different structures and to determine kinetics of the peptide release from these hydrogels using an in vitro model. Isotropic and macroporous hydrogels based on poly(vinyl alcohol) acrylic derivative (Acr-PVA) and also macr...

In this study, two novel chitosan-graft-poly(vinyl alcohol) copolymers are synthesized and used as water-soluble at physiological conditions polycations for preparation of smart microcapsules. The microcapsules provide growth and proliferation of eight mammalian cell lines, including hybridoma and tumor cells, at long-term cell cultivation in vitro...

Multi-component reactions of building blocks with more than one MCR-reactive group will give rise to oligomeric MCR products. The proper choice of at least two bifunctional building blocks will give either a polymeric or a cyclic product. Apart from polymerization, repetitive or consecutive Ugi reactions have been used to produce linear MCR-heteroo...

In the current study, semi-permeable alginate-oligochitosan microcapsules for multicellular tumor spheroids (MTS) generation were elaborated and tested, to estimate a response of the microencapsulated MTS (MMTS) to photodynamic therapy (PDT). The microcapsules (mean diameter 600 μm) with entrapped human breast adenocarcinoma MCF-7 cells were obtain...

We demonstrate a new one-batch approach to the fabrication of a biocompatible Ca-alginate film with embedded vitamin E-loaded microspheres that could be used for planar dermal drug delivery. Stable vitamin E microspheres, coated with gum acacia, are produced by ultrasonic treatment of a two-phase liquid system. The Fourier transform infrared spectr...

In the current study a technique for microencapsulation of human breast adenocarcinoma cells MCF-7 in alginate-chitosan microcapsules is used. Microencapsulation is proposed to generate multicellular tumor spheroids (MTS) based on these cells and to test them further as an in vitro model for anti-tumor drug screening. Cytotoxicity of methotrexate (...

To generate multicellular tumor spheroids (MTS) based on human breast adenocarcinoma MCF-7 cells and to study them as a novel in vitro model for anticancer drug screening, a technique for cell microencapsulation in biocompatible alginate-chitosan microcapsules has been used in this study. Using the MTS based on the MCF-7 cells methotrexate (MTX) cy...

Nanoemulsions of the water in oil type (w/o) composed of nontoxic components, including low concentrations of AOT (5%) and soy-bean lecithin Lipoid S100 (10%) in eucalyptus oil and limonene, were developed and characterized. These nanoemulsions can be used for the incorporation of biomolecules. As shown, AOT based systems possessed the highest solu...

Chemico-enzymatic methods are a promising approach to obtain various biologically active compounds, including enantiomerically pure substances. Entrapment in gels is one of the most convenient methods to stabilize enzymes for their application in water/organic media. In this study, proteases (trypsin and chymotrypsin) were entrapped into a composit...

Biodegradable microparticles based on poly-D,L-lactide with entrapped mixture of herbal water-soluble extracts of Plantago major and Calendula officinalis were prepared. For preparation of these microparticles the previously developed method based on the usage of supercritical carbon dioxide (SC-C02) was proposed. Microparticles were obtained by tw...

In this study an universal method for preparation of biodegradable microcapsules for antigen entrapment was proposed and optimized. The multilayer microcapsules were prepared by layer-by-layer adsorption of various polyelectrolytes (such as alginate, poly-L-lysine, κ-carrageenan, chitosan and dextran derivatives). High entrapment efficiency of prot...

A general method for the preparation of biodegradable microcapsules capable of antigen inclusion is suggested. Multilayer microcapsules were obtained by the method of level-by-level sorption of various polyelectrolytes (alginate, poly-L-lysine, kappa-carrageenan, and chitosan and dextran derivatives). High inclusion efficiency was found for protein...

Introduction Since Sutherland developed the multicellular tumor spheroid (MTS) model to mimic the 3D-structure of small size solid tumors (R. Sutherland et al., 1970), MTS have been found to be useful in several aspects of tumor biology, including studies in the field of radiation biology and photodynamic therapy (PDT). Cellular organization of MTS...

Potentially hemocompatible alginate-chitiosan microparticles and microcapsules coated with a semipermeable membrane with incorporated glycoconjugates were synthesized. The membrane acts as a barrier, which keeps the incorporated glycoconjugate from going outside but permits antibodies to penetrate inside and specifically bind to antigens, high-mole...

The microcapsules with entrapped herbal water-soluble extracts Plantago major and Calendula officinalis L. (HE) were prepared by LbL-adsorption of carrageenan and modificated chitosan onto CaCO3 microparticles with their subsequent dissolving after the treatment of EDTA. Entrapment of HE was performed by adsorption and co-precipitation techniques....

Based on the method of the layer-by-layer (LbL) adsorption of oppositely charged polyelectrolytes, sodium alginate (Alg) and poly-L-lysine (PLL), novel biodegradable microcapsules have been prepared for delivery of biological active substances (BAS). Porous spherical CaCO3 microparticles were used as templates. The template cores were coated with s...

Novel biodegradable microcapsules for delivery of biologically active substances (BAS) were prepared by layer-by-layer (LbL) adsorption of oppositely charged polyelectrolytes, namely sodium alginate (Alg) and poly-L-lysine (PLL). To immobilize these BAS, porous spherical CaCO3 microparticles were used as templates. The templates (cores) were coated...

Self‐disintegrating microcapsules were prepared by encapsulating a highly active mix of proteases (Pronase®) into biodegradable polyelectrolyte shells. Pronase was captured by micron‐sized calcium carbonate particles that were subsequently embedded into onion‐like shells of poly( L ‐arginine) and poly( L ‐aspartic acid). EDTA treatment was used to...

The methods of animal cell immobilization in chitozan microcapsules and alginate polyethylene glycol microgranules and their in vitro maintenance are presented. Hybridoma SS-3 cells remained viable for at least 20 days and capable of producing IgG immunoglobulins, which penetrate through an alginate-chitosan membrane.

Thrombin receptor agonist peptide (TRAP-6) could advantageously replace thrombin in terms of accelerating wound healing being less expensive and more stable. To promote TRAP-6 pharmacological action as a tissue reconstruction stimulator this study investigated its entrapment within poly(D,L)-lactide-co-glycolide (PLGA) microparticles. Due to its lo...

Thrombin receptor agonist peptide (TRAP-6) may effectively replace thrombin for stimulation of damaged tissue regeneration. (Thrombin employment is limited by its high cost, instability and proinflammatory effect at high concentrations.) Immobilization of TRAP-6 into a poly(D,L)-lactide-co-glycolide (PLGA)-based matrix can protect peptides from a d...

The aim of the current paper was to elaborate an immobilization method of thrombin receptor agonist peptide (TRAP-6) in biodegradable biocompatible poly(d,l)-lactide-co-glycolide (PLGA) microparticles and to demonstrate the effect of the entrapped peptide for tissue repair, namely for a gastric ulcer treatment in rats. TRAP-6 was entrapped in polym...

The effect of synthetic thrombin receptor (PAR1) agonist peptide encapsulated in microspheres made of lactic and glycolic acid copolymer on tissue reparation was studied in rats with acetate-induced ulcer. PAR1 agonist peptide was immobilized in biodegraded lactic and glycolic acid microspheres by double emulgation, the kinetics of peptide release...

Chemo-enzymatic methods constitute a promising approach to obtain various biologically active compounds, including enantiomerically pure substances. Entrapment in gels is one of the most convenient methods to stabilize enzymes for their application in water/organic media. Proteases and lipases are widely used for enantioselective transformations of...

Over the past several decades bioencapsulation has become one of the most promising techniques in various biomedical fields. Bioencapsulation is considered as special techniques for preparation of different polymer systems (hydrogel micro-and nanoparticles, as well as microparticles or micra- capsules, etc.) with entrapped biomaterial, such as biol...

PAR1 peptide thrombin receptor agonist (PAR1-AP) was encapsulated in microcorpuscles based on lactic and glycolic acid copolymer. The desorption profile of the preparation was studied in vitro and its wound-healing effects were studied on a model of cut skin wound in mice. The study showed that 90% PAR1-AP was desorbed over 6 h, but the peptide was...

Due to a great recent progress in animal cell biotechnology in particular in gene engineering, large-scale production of important biological materials, such as viral vaccines, viral vectors, as well as various cell products has become an industrial reality. The list of these products includes recombinant proteins and peptides, lymphokines and cyto...

Presently multicellular tumor spheroids (MTS) are being widely used in various aspects of tumor biology, including studies in biology and photodynamic therapy. The cellular organization of spheroids allows the recreation of in vivo small tumors much better than all common two-dimensional in vitro models. The cell encapsulation method could be propo...

Polymer dressings with encapsulated thrombin or synthetic peptides which can mimic thrombin action are employed for wound healing. Paper describes the method for preparation of these hydrogel composites of PVCL-CaAlg [poly(N-vinyl caprolactam-calcium alginate). The effect of encapsulated thrombin/peptides on tissue repair process have beet investig...

Polymer dressings with encapsulated thrombin or synthetic peptides which can mimic thrombin action are employed for wound healing. Paper describes the method for preparation of these hydrogel composites of PVCL-CaAlg [poly(N-vinyl caprolactam-calcium alginate). The effect of encapsulated thrombin/peptides on tissue repair process have beet investig...

To accelerate the healing processes in wound repair, attempts have been repeatedly made to use growth factors including thrombin and its peptide fragments. Unfortunately, the employment of thrombin is limited because of its high liability and pro-inflammatory actions at high concentrations. Some cellular effects of thrombin in wound healing are med...

Some aspects of the suitability of alginate beads entrapping Chlamydomonas reinhardtii cells for nitrate consumption from nitrate-containing waters were studied and discussed. Among 14 different metal cations tested as gel bead stabilizing agents, only calcium and barium formed beads showing nitrate-consuming activity. Pure calcium alginate cell en...

A one-step mild method for entrapping animal cells and enzymes in macroporous composite poly (N-vinyl caprolactam)-calcium alginate (PVCL-CaAlg) hydrogels is described. Some properties of immobilized enzymes, such as thermal and storage stabilities and stability in water/organic media were investigated. Composite PVCL-CaAlg gels were successfully a...