Jano Markhulia

The most conventional method for obtaining Fe3O4 or γ-Fe2O3 is chemical co-precipitation. In our work, we propose a simple and cost-effective method for obtaining colloidal suspensions composed of Fe3O4 nanoparticles coated with CA and dispersed in a liquid carrier (distilled water). Our particles were synthesized by chemical co-precipitation with ultrasonication (sonolysis) in a low vacuum environment [1,2]. Before coating with CA, the obtained IONPs were processed by electrohydraulic discharges in the high discharge current (HC) (several tens of Amperes) and low discharge current (LC) (several Amperes) modes in water medium using pulsed direct current (PDC). X-ray Powder Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), Dynamic Light Scattering (DLS), Ultraviolet-Visible Spectroscopy (UV VIS), and Small Angle X-Ray Scattering (SAXS) were used to characterize the obtained samples.

Breast cancer is the most commonly diagnosed tumor formation in women around the world, which is also the leading cause of female cancer mortality. Although significant progress has been made in the diagnosis and therapy of breast cancer, early detection of disease and antimetastatic treatment still remain a serious problem. The development of the next generation of cancer therapy modalities is relevant in modern oncology. Nanotechnology offers promising prospects in this direction. Recently, the uptake of multifunctional iron oxide nanoparticles, combining both therapeutic and diagnostic capabilities, is gaining increasing attention in terms of cancer treatment, diagnosis, and targeted drug delivery. This study is dedicated to the synthesis of Citric acid-modified Superparamagnetic Iron Oxide Nanoparticles (SPIONs) functionalized with an anti-cancer drug Doxorubicin (DOX), using a controlled chemical co-precipitation method and study in vitro cytotoxicity of obtained magnetic nanofluids (containing Bare, Citric acid-coated, and DOX-loaded IONPs) on 4T1 tumorigenic epithelial cell lines (Figure 1). The synthesized samples were characterized using X-ray diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), Small-Angle X-ray Scattering (SAXS), Vibrating Sample Magnetometry (VSM), and UV-VIS spectrophotometry. To properly analyze and understand the behavior of 4T1 cancer cells after administrating Bare, Citric acid modified, and DOX-loaded IONPs in comparison with free DOX, a complex set of in vitro tests were used, including MTT assay, determination of the cell cycle, and IONPs uptake. Synthesized magnetic nanofluids containing Iron ox-ide nanoparticles (both Bare and modified with citric acid), revealed cytotoxicity on 4T1 cancer cells. However, the results showed the advantage of a combination of doxorubicin and magnetic nanoparticles. The DOX-loaded IONPs were more able to inhibit the growth and proliferation of 4T1 breast cancer cells in vitro, indicating that the system has the potential to act as an antitumor chemotherapeutic agent.

Among the broad range of nanoscale materials such as Fe3O4, γ-Fe2O3, CоFe2O4, ZnFe2O4, and BaFe12O19 investigated for biomedical use. Superparamagnetic nanoparticles (SPIONs) of magnetite (Fe3O4) and maghemite (γ-Fe2O3) have attracted significant attention due to their biocompatibility and good magnetic properties, which implies their sensibility to applied external magnetic fields. They can be applied in multifunctional approaches by encapsulation of the particles with a suitable coating substance [1, 2] for controlled drug delivery of therapeutic agents in vivo applications [3]. Other applications are found in the area of magnetic resonance imaging, tissue repair, immune analysis, biological fluids detoxification, magnetic hyperthermia, and cell separation. A simple and cost-effective method was developed to obtain Folic Acid (FA) - conjugated Magnetic Nanoparticles (MNs). Colloidal suspensions composed of a single domain of superparamagnetic iron oxide nanoparticles (SPIONs) dispersed in a liquid carrier (distilled water) were synthesized by in-situ co-precipitation and ultrasonication (sonolysis) in a vacuum environment (0.98 Mpa). Before conjugation was obtained MNs were processed by electrohydraulic discharges (see Fig. 1.) in two modes: the high discharge current (HC) (several tens of Amperes) and low discharge current (LC) (several Amperes) mode in an aqueous system using a pulsed direct current (PDC). The processing was performed in a low-pressure reactor at high voltage (1-1.5 kV). HC and LC mode regulated by the distance between discharge rods (from 1.5 to 3 mm). The X-ray Powder Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), Dynamic Light Scattering (DLS), Ultraviolet-Visible Spectroscopy (UV-VIS), Vibrating Sample Magnetometry (VSM), Small Angle X-Ray Scattering (SAXS) and Small-Angle Neutron Scattering (SANS) were used to characterize obtained samples.

Iron oxide nanoparticles (IONPs) are of great interest for researchers working in different fields of physics, chemistry, biology, and medicine. Growing interest is based on their physical-chemical and pharmacokinetic properties. A well-known method of synthesis of IONPs is chemical co-precipitation. Although this method is distinguished by its simplicity, cheapness, and the possibility of producing in a largescale, its main drawback is that it is impossible to uniformly distribute the concentrations of reactants, and control the nucleation and crystal growth. Small-angle neutron scattering (SANS) and small-angle X-ray scattering (SAXS) were used for the determination of the microscale or nanoscale structure of particle systems in terms of average particle sizes, shapes, size distribution, and surface-to-volume ratio. Additional information was obtained on the colloidal stability, the quality of the dispersion, and the amount and character of the possible particle aggregation. We used Dynamic light scattering (DLS) technique to determine the size distribution profile of small particles in suspension in order to calculate hydrodynamic radius of aspheres. For assessment of stability of colloidal dispersions, we measure the zeta potential of the samples. The magnitude of the zeta potential indicates the degree of electrostatic repulsion between adjacent, similarly charged particles in a dispersion. The proposed approach, as shown by preliminary studies, significantly improves the dispersion of the solution. Strong oscillations associated with the electrohydraulic effect, additionally disperse the chemically synthesized particles. In the present work, we overview trends of the technique of nanomaterial production and processing by pulsed high voltage discharge in solution/water. This work is supported by National Shota Rustaveli National Science Foundation (Grants # # PhDF2016–59 and Ys17–15) and by Central European Research Infrastructure Consortium (Elettra – Proposal No: 20177016).

We propose electrohydraulic discharges assisted chemical co-precipitation technique in order to develop a simple, cost-effective, large-scale manufacturing of bio-applicable iron oxide nanoparticles involving plasma arc discharges in base solution. By this method, as preliminary experiments shows, we obtain better dispersing the formed nanoparticles at the initial stage, process their surface (static stabilization, H and OH radical addition for better absorbance) by pulsed discharges, and add to the fluid the bactericidal properties. After that, the covering (stabilizing) of the monodisperse nanoparticles with surfactant is relatively easy to follow, with bioactive molecules (dextran, polyvinyl alcohol, polyethylene glycol, etc.), followed by washing from chemical reaction residuals, additional ultrasound homogenization, and centrifugation.

Transition electron microscopy, vibrating sample magnetometer, VIS spectrophotometry, and bactericidal research was used to characterize obtaining samples. 

Surface-modified superparamagnetic iron oxide nanoparticles (SPIONs) are a kind of novel functional materials, which have been widely used in various areas. The main requirements to magnetic nanoparticles for biomedical applications are the nontoxicity, biocompatibility and high-level accumulation in the target tissue or organ, chemical stability, simplicity and reproducibility of synthesis. The composition and characteristics of the SPION surface have a strong influence on their stability, distribution, and biocompatibility, with regard to cellular uptake and cytotoxicity. This study is focused on the development of the synthesis of aqueous suspensions of SPIONs stabilized with hydrophilic polymer - polyethylene glycol (PEG). Iron oxide nanoparticles were synthesized via a controlled co-precipitation technique in the vacuum environment. Crystalline structures and particle sizes obtained iron oxide nanoparticles were characterized using X-ray diffraction (XRD) and Transmission Electron Microscopy (TEM). Magnetic properties were studied using the Vibrating Sample Magnetometer (VSM). Also, investigated the influence of PEG-coated SPIONs on the viability of the bacterial colonies of the Staphylococcus epidermidis. The detected bactericidal effect was time and growth phase-dependent. The outcomes of this study will further lead to the possible application of SPIONs for human chronic wound healing.

Iron oxide nanoparticles containing in magnetic fluids are used in a rapidly expanding number of research and practical applications in the biomedical field of magnetic resonance imaging (MRI) contrast enhancements, direct drug delivery systems, hyperthermia treatment as well as labeling and separation of biological materials. In the last decade, increased investigations with several types of iron oxides have been carried out in the field of magnetic NPs, among which magnetite (Fe3O4) and maghemite are the very promising and popular candidates since their good biocompatibility. The main technological challenges are related to the improvement of the following properties: precise control of size, shape, stability, and dispersibility of NPs in desired solvents.

This review is focused on the synthesis of superparamagnetic iron oxide nanoparticles (SPIONs). Iron oxide nanoparticles coated with PVA4–88 were synthesized by two methods: In the first case, iron oxide nanoparticles coating with PVA4–88 are carried out after the synthesis of the magnetic nanoparticles, and in the second case - in the synthesis process. In both cases, the Iron oxide nanoparticles were synthesized by suitable modification of the standard synthetic procedure with a controlled co-precipitation technique in one-pot in a vacuum environment. A Co-precipitation technique under a vacuum environment was used to prevent undesirable critical oxidation of Fe2+. The obtained PVA-coated biocompatible 10-20 nm-sized nanoparticle dispersive solution with pH ≈ 7.4 and solid phase content ranging from 0.02-1 % w/v. Prepared iron oxide nanoparticles were characterized using X-ray diffraction (XRD). Particle sizes measured from TEM are approximately 10–20 nm, and the magnetic cores exhibit somewhat irregular shapes varying from spherical, oval, to cubic. Also has been investigated magnetic properties. The Vibrating Sample Magnetometer (VSM) studies indicate the presence of superparamagnetic nanoparticles in a magnetic ferrofluid and surfactant influence on the characteristic of the magnetization at room temperatures into high and low magnetic fields.  

This work was supported by Shota Rustaveli National Science Foundation (Grant No. PhDF2016_59)

 In this work magnetic nanofluids containing polyethylene glycol (PEG), coated iron oxide nanoparticles were synthesized by a controlled chemical co-precipitation method.

The synthesized nanomaterial was studied by a Transmission Electron Microscope, X-ray diffraction, and a Vibrating Sample Magnetometer. Also, the obtained polymer-coated iron oxide nanoparticles were tested for bactericidal effects on Staphylococcus epidermidis. 

Established morphology, structural content, magnetic properties, and size distribution of obtained nanomaterial.

According to bactericidal studies, the PEG-coated Fe3O4 nanoparticle has a bactericidal effect. It is shown that this effect depends on the phase of bacterial growth. 

We consider the effect of nano Fe3O4 doping on the superconducting properties of MgB2. To do this, we for the first time turn on the electrohydraulic effect (Yutkin effect) [4] in a well-known scheme for the treatment (synthesis) of nanoparticles in order to significantly reduce the departure from the average size of particles and for ensuring the reproducibility of the synthesis process of the composite MgB2- Fe3O4. Nano- Fe3O4 (of various sizes) doped polycrystalline MgB2 samples were synthesized by encapsulation of well-mixed high-quality Mg, B, and nano- Fe3O4 powders. In order to study the effect of magnetic particles on superconductivity, the composites of (MgB2)0.98(Fe3O4)0.02 was synthesized with former sintered at different temperatures. The superconducting properties were investigated in the case of samples sintering at high temperatures (7500C) and at low temperatures (3500C). We have investigated the effect of the addition of several concentrations of magnetite Fe3O4 nanoparticles on the microstructure, critical temperature Tc, and the critical current density Jc in the composite MgB2-Fe3O4 material. The study was conducted using X-ray Diffraction (XRD), Energy Dispersive X-Ray Spectroscopy (EDS), and a vibrating sample magnetometer (VSM) for the magnetization measurements. 

Developed the original technology of the synthesis and stabilization of magnetic fluid for biomedical applications, containing magnetite (Fe3O4) nanoparticles, stabilized by different surfactants and investigated their magnetic and optical properties. Considered the role of the electrohydraulic methods for uniform and highly distribution in size of magnetic particles in ferrofluids. Also investigated stabilization of magnetic nanoparticles coated with various biocompatible surfactants (PEG 4000, PEG 6000) treated by ultrasound. By the vibrating sample magnetometer, at room temperature is measured the magnetization of magnetic particles of untreated and treated by ultrasound and electrohydraulic method. Based on the analysis it is shown the effect of this treatment is on the magnetization of nanofluids. Also studied the role of surfactant molecules on the distribution of ferromagnetic nanoparticles in the dispersion medium.

The development of the synthesis of stable aqueous suspensions of superparamagnetic iron oxide nanoparticles stabilized with unmodified polyethylene glycol (PEG) at two molecular weights (4000 and 6000 Da) and dextran-40 has been reported. The obtained biocompatible polymer (PEG)m and dextran-coated nanoparticle dispersive solution with pH  6.5 and solid phase content ranging from 0.02-0.75 % w/v has been investigated for optical and magnetic properties. Biomedical application requires the biocompatible superparamagnetic iron oxide nanoparticles (SPION), which are stable and well dispersed in water at physiological pH or in physiological salinity. Biocompatible 10-20 nm sized SPIONs have been synthesized via co-precipitation method in the vacuum environment. These SPIONs have been modified with PEG and dextran in a one-pot synthesis. Vibrating Sample Magnetometer (VSM) studies show the effect of phase transformations on the magnetic properties of the nanoparticles and surfactant influence on the characteristic of the magnetization at room temperatures into high and low magnetic fields.

The development of the synthesis of stable aqueous suspensions of superparamagnetic iron oxide nanoparticles stabilized with unmodified polyethylene glycol (PEG) at two molecular weights (4000 and 6000 Da) and several PEG/iron ratios have been reported. The obtained biocompatible polymer (polyethylene glycol -PEG) coated nanoparticle dispersive solution with pH ≈ 6.5 and solid phase content ranging from 0.02-0.75 % w/v has been investigated for optical and magnetic properties. The biomedical application requires biocompatible superparamagnetic iron oxide nanoparticles (SPION), which are stable and well dispersed in water at physiological pH or in physiological salinity. Biocompatible 10-20 nm-sized SPIONs have been synthesized via the co-precipitation method in the vacuum environment. These SPIONs have been modified with PEG in a one-pot synthesis. Vibrating Sample Magnetometer (VSM) studies show the effect of phase transformations on the magnetic properties of the nanoparticles and surfactant influence on the characteristic of the magnetization at room temperatures into high and low magnetic fields.

Magnetic nanoparticles have shown great potential in many biological and biomedical applications such as targeted drug delivery, magnetic fluid hyperthermia, magnetic resonance imaging, and tissue engineering. All these applications require magnetic nanoparticles to be water-soluble and biocompatible. For biological and biomedical applications, magnetic iron oxide nanoparticles are the primary choice because of their biocompatibility and chemical stability. Many synthesis methods have been explored for magnetic iron oxide nanoparticles. These include an organic solvent heating method, polyol method, and co‐precipitation method. The co‐precipitation method is the most effective technique for preparing aqueous dispersions of iron oxide nanoparticles because the synthesis is conducted in water. For this report, we studied several biological molecules as surface coatings to achieve biocompatibility such as ascorbic acid, polyvinyl alcohol, poly(ethylene glycol), and dextran. These molecules were used to control the particle size, prevent the nanoparticles from aggregating, and achieve biocompatibility. 

The most conventional method for obtaining Fe3O4 is by co-precipitation. The size and shape of the iron oxide NPs depend on the type of salt used, the ferric and ferrous ions ratio, the reaction temperature, the pH value, ionic strength of the media, and the other reaction parameters. 

But this method needs to be improved in order to raise monodispersity that is necessary in the case of biomedical applications. To do this, we for the first time turn on the electrohydraulic effect in a well-known scheme for the treatment of nanoparticles in order to significantly reduce the scatter radius of particles. To do this, we have a device created by us that is stationary pilot equipment. As a result, the size radius of particles becomes almost the same and the particle solubility in water is increased. 

We carried out preparation of the magnetic colloid by an adapted co-precipitation method in the presence of an electrohydraulic effect, with further magnetite stabilization. The samples are analyzed by VSM at room temperature to find the saturation magnetization of ascorbic acid-coated iron oxide NPs. 

In the manufacture of magnetic fluid for medical purposes, which is a colloidal dispersion with a volume fraction of particles of 25%, it is necessary to solve several problems: firstly, it is necessary to obtain small (8 - 15 nm) magnetic particles and it is necessary to cover the particles of the dispersed phase, which should prevent particles from sticking together among themselves, and should also ensure the formation of a stable colloidal system of single-layer magnetic particles dispersed in the carrier liquid. Modern dispersion methods, such as ultrasonication and centrifugation, partially provide an average degree of dispersion, which is manifested in the separation of particles that have entered the liquid, but the reduction of already formed large particles (20 to 80 nm in size) is a complex process. and requires high binding energy. The advantage of electrohydraulic treatment of chemically obtained Fe3O4 nanoparticles by the electrohydraulic method over the methods of centrifugation and ultrasonic treatment for better dispersion and size uniformity is proposed. The essence of this method is the implementation of an electric discharge in a liquid in a closed or open vessel, with a special impulse, as a result of which a high hydraulic pressure arises around the discharge zone, which performs useful mechanical work, in our case, mechanical crushing. Resonance processes and powerful infra- and ultrasonic vibrations additionally disperse and crush large particles, thereby increasing the sorption properties of the particles.

The chemical coprecipitation method for the obtaining of magnetic nanoparticles developed by us with two-step synthesis technology is a processed method for the production of magnetite (Fe3O4) nanoparticles, which includes both the chemical method of obtaining nanoparticles with scrubbing procedures. Placing in a liquid. This complex method is generally considered to give small sizes of finely dispersed nanoparticles and is distinguished by a relatively high stabilization in the transfer fluid. Added to all this is the non-toxicity and biocompatibility of the selected material, which is a prerequisite for medical use.

The most conventional method for obtaining Fe3O4 or γ-Fe2O3 is chemical co-precipitation. In our work we propose a simple and cost-effective method for obtaining colloidal suspensions composed of Fe3O4 nanoparticles coated with CA and dispersed in a liquid carrier (distilled water). Our particles were synthesized by chemical co-precipitation with ultrasonication (sonolysis) in a low vacuum environment [1,2]. Before coating with CA, the obtained IONPs were processed by electrohydraulic discharges in the high discharge current (HC) (several tens of Amperes) and low discharge current (LC) (several Amperes) modes in water medium using pulsed direct current (PDC). X-ray Powder Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), Dynamic Light Scattering (DLS), Ultraviolet-Visible Spectroscopy (UV VIS), and Small Angle X-Ray Scattering (SAXS) were used to characterize the obtained samples.

Doctoral Thesis Referee

Master Theses Supervisor

Doctoral Thesis Supervisor/Co-supervisor

Scientific editor of monographs in foreign languages

Scientific editor of a monograph in Georgian

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Review of a scientific professional journal / proceedings

Member of the editorial board of a peer-reviewed scientific or professional journal / proceedings

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Research articles in high impact factor and local Scientific Journals

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