Modified alginate hydrogels are of interest for potential use in medical applications in the field of drug delivery due to their biocompatibility and the ability to encapsulate various substances. This work focuses on alginate hydrogels and their modification with hydroxyapatite, with the objective of developing yttrium-90 carriers for nuclear medicine applications. In the course of this work, beads based on calcium and yttrium alginate modified with hydroxyapatite by enzymatic synthesis are produced for the first time. The beads are characterized using optical and electron microscopy, IR and Raman spectroscopy, X-ray diffraction and analytical methods. The swelling kinetics of the beads are investigated, as this may provide insight into the potential therapeutic embolic effect. Yttrium-containing alginate beads swell to 10 % of their initial volume, while calcium beads swell to almost their initial size in saline. Various ways of incorporating yttrium-90 into the beads are discussed, including the cross-linking reaction during the synthesis or sorption and isotope exchange on produced beads. These processes are studied using spectrophotometry and liquid scintillation counting. The sorption values approach the limiting values in 4-5 h. Mineralization has been demonstrated to enhance the sorption capacity of the wet beads, with values reaching 45 mg g-1. 89Y-90Y isotope exchange for yttrium alginate and [90Y]YNO3 solution results in equal isotope redistribution within a period of four hours. A minor release of yttrium, amounting to approximately 1 % in serum, was observed after 48 h for mineralized beads. The results demonstrate the fundamental possibility of using alginate-hydrogel based materials as radionuclide carriers in nuclear medicine.
This work is devoted to iron alginate and hydroxyapatite composites as potential 32P carriers for nuclear medicine applications. As a result of this work beads cross-linked with trivalent iron and modified using hydroxyapatite were synthesized for the first time. The beads were characterized using optical and electron microscopy, X-ray diffraction, EDX and IR spectroscopy. A method for introducing 32P into beads by sorption of phosphate ions from a solution was proposed. The physicochemical parameters of this process were studied using spectrophotometry and liquid scintillation counting. The incorporation of the mineral phase into iron alginate beads resulted in an enhancement of the sorption capacity towards phosphate ions from 25 to 45 mg∙g-1. Furthermore, mineralization has been demonstrated to improve the kinetic parameters of phosphate sorption due to the additional binding sites and the isotope exchange process. Sorption values approach the maximum 1 h after the start of the experiment for the best sample. Composite beads based on iron alginate and hydroxyapatite exhibited enhanced radionuclide retention in aqueous media, saline solution, and blood serum when compared to unmodified iron alginate beads. Advancements in the retention properties of the beads post-drying were exhibited. The optimal beads, derived from iron alginate and hydroxyapatite, as obtained in acetate buffer, exhibited a 23 % release of 32P in blood serum at 36.6 °C within a 30-day period. The results demonstrate the potential of iron alginate and hydroxyapatite composites as 32P carriers in nuclear medicine.
Chromium has limited solubility in -iron. It is shown that unsaturated Fe-Cr alloys should demonstrate short-range ordering (i.e. tendency to neighboring of Fe and Cr atoms). The type of short-range ordering in several Fe-Cr alloys is revealed from the data on the recovery of residual electrical resistivity after low temperature electron irradiation at sufficiently low temperatures. The combined consideration of the data on short-range ordering and chromium solubility at 570 K (Scr. Mater. 2014 v. 74, p. 48 and ibid 2016 v. 122, p. 31) gives the confidence interval for the solubility limit near 270 K equal to 8.8±0.4 at. % Cr.
The paper presents data on electrical resistivity recovery in the Fe-13.4Cr and Fe13.6Cr-1.9Si alloys during isochronal annealing after 5 MeV electron irradiation below 77 K. Long-range migration of radiation-induced defects starts slightly above 200 K in Fe-13.4Cr. The silicon addition in Fe13.6Cr-1.9Si leads to immobilization of Frenkel pair defects thus making the peaks of the stages of the onset of long-range migration shift towards high temperatures up to 370 K and 420 K for self-interstitial atoms and vacancies, respectively. This finding confirms the data obtained earlier for Fe16Cr-Si alloys by means of positron annihilation technique (JNM 508(2018) 100–106) on trapping of radiation-induced defects on Si agglomerates (clusters consisting of several silicon atoms) formed during defect migration.
The short-range clustering enhanced by migration of non-equilibrium point defects generated under the high-pressure torsion in Bridgman anvils and ball milling is detected by means of Mossbauer spectroscopy in Fe100-cCrc (c = 12-20.6) binary alloys. The degree of short-range clustering is increased with increasing the temperature of severe plastic deformation. The short-range clustering enhanced by severe plastic deformation is similar to that obtained after the thermal annealing and electron irradiation at close temperatures.
Modification of the cocrystallization method for producing hydroxyapatite (HAP) and an HAP-Cu combination to the enzymatic method using alkaline phosphatase leads to a change in the morphology, sizes, sorption capacity, type of particles, and conformity with the Langmuir and Freundlich models. A positive factor of the enzyme usage is an increase in the sorption capacity and the possibility to strictly control the particle sizes depending on the concentration of the enzyme used. The L 2 CuCl 4 complex was synthesized on the basis of 2-aminopyrimidine (L), which is the precursor of many anticancer drugs, and the possibilities of introducing L 2 CuCl 4 into the HAP composite were considered. The cytotoxicity data for various HAP and L 2 CuCl 4 composites with respect to various types of leukemic cells as compared to lymphocytes of healthy donors showed antileukemic activity of the copper complex and the absence of HAP cytotoxicity in a wide range of concentrations.
Использование наночастиц как носителей лекарственных средств широко изучается. Одним из важных вопросов остается изменение размеров и цитотоксических свойств частиц в процессе их получения и применения. Целью работы было исследовать возможную агрегацию [67Zn]порфиринфуллерен-наночастиц (BFNP) в зависимости от времени и провести сравнительный анализ свойств наночастиц гидроксиапатита (HAP), полученных различными способами. Оказалось, что агрегация BFNP качественно не влияет на функцию наночастиц, но количественно уменьшает их воздействие на лейкемические клетки. Варьирование способов получения и обработки наночастиц НАР позволяет менять их форму, размеры и сорбционную способность по отношению к ионам металлов, а также лигандам и комплексам. Используя ферментативный метод, мы получили НАР с заранее заданными свойствами путем варьирования условий синтеза. Полученные наночастицы НАР представляют собой радиопрепараты, содержащие короткоживущие изотопы цинка и меди (в виде ионов и соединений — производных тиазина и пиримидина). Эти наноконструкции содержат два антиопухолевых компонента (радионуклид и лиганд или комплекс), что определяет их фармакологический потенциал для диагностики и лучевой терапии.
The size control of materials is of great importance in research and technology because materials of different size and shape have different properties and applications. This paper focuses on the synthesis of hydroxyapatite in ultrasound fields of different frequencies and intensities with the aim to find the conditions which allow control of the particles size. The results are evaluated by X-ray diffraction, Transmission Electron Microscopy, morphological and sedimentation analyses. It is shown that the hydroxyapatite particles synthesized at low intensity non-cavitation regime of ultrasound have smaller size than those prepared at high intensity cavitation regime. The explanation of observed results is based on the idea of formation of vortices at the interface between phosphoric acid and calcium hydroxide solution where the nucleation of hydroxyapatite particles is taken place. Smaller vortices formed at high frequency non-cavitation ultrasound regime provide smaller nucleation sites and smaller resulting particles, compared to vortices and particles obtained without ultrasound. Discovered method has a potential of industrial application of ultrasound for the controlled synthesis of nanoparticles.
Nanoparticles for drug delivery are the subject of extensive research. Importantly, they can transform in size during synthesis or actual use, thereby changing their cytotoxic properties. The aim of the present work was to study the tendency of [67Zn] porphyrin-fullerene nanoparticles (BFNP) to aggregate over time and to compare the properties of hydroxyapatite (HAP) nanoparticles obtained through 3 different techniques. We found that aggregation of BFNP nanoparticles does not affect their function but attenuates their cytotoxicity against leukemia cells. We were also able to obtain HAP nanoparticles with programmable properties (such as size, shape or the capacity to adsorb metal ions, ligands and chemical complexes) through enzymatic synthesis by varying its conditions. The synthesized HAP nanoparticles contain short-lived isotopes of zinc and copper (in the form of ions and complexes with pyrimidine or thiazine derivatives). These tumoricidal components (a radionuclide and a ligand or a complex) determine the diagnostic and therapeutic potential of the obtained radiopharmaceutical agents.
The method of resistivity recovery is a powerful tool for studying point defects in irradiated metals. However, the method is nonspecific with respect to a type (vacancy or interstitial) of investigated defects. To overcome this shortcoming, we made use of opposite signs of excess electric charges of the vacancies and self-interstitial atoms in a lattice. Resistivity loss takes place on trapping of vacancies at impurity atoms if excess charges of the impurity atom and defect are opposite in sign. A way of selecting the impurity atoms with the excess charge opposite in sign to that of vacancies is proposed. The specific evolution of resistivity recovery spectrum induced by vacancy trapping at the selected impurity atoms (probe traps) allows one to unambiguously identify the stage of free long-range vacancy migration.
The effect of Si concentration (0.2, 0.75 and 1.5 at.%) on properties of vacancy type defects formed under 5 MeV electron irradiation near 300 K in Fe-16 at.% Cr matrix has been studied by means of angular correlation of annihilation radiation technique. It is found that vacancy clusters are accumulated in Fe16Cr and Fe16Cr-0.2Si. Accumulation of monovacancies and their decoration with Si atoms are observed in Fe16Cr-1.5Si. Accumulation in Fe16Cr-0.75Si demonstrates transient features. Postirradiation annealing kinetics in Fe16Cr and Fe16Cr-0.2Si differs from that in Fe16Cr-0.75Si and Fe16Cr-1.5Si. Annealing of vacancy clusters takes place in Fe16Cr and Fe16Cr-0.2Si, while vacancy clusters form and start annealing in Fe16Cr-0.75Si and Fe16Cr-1.5Si above 425 K. It is concluded that Si atoms aggregates are formed in Fe16Cr-0.75Si and Fe16Cr-1.5Si under irradiation, which capture monovacancies and hold them up to 425 K. Mechanism of Si aggregate formation is discussed based on published data on interaction between vacancies and atoms of Si in Fe-Si alloys. (C) 2018 Elsevier B.V. All rights reserved.
In this study, we report a method for the suppression of Escherichia coli (E. coli) vitality by means of therapeutic ultrasound irradiation (USI) using biocompatible silicon nanoparticles as cavitation sensitizers. Silicon nanoparticles without (SiNPs) and with polysaccharide (dextran) coating (DSiNPs) were used. Both types of nanoparticles were nontoxic to Hep 2 cells up to a concentration of 2 mg/mL. The treatment of bacteria with nanoparticles and application of 1 W/cm2 USI resulted in the reduction of their viabilities up to 35 and 72% for SiNPs and DSiNPs, respectively. The higher bacterial viability reduction for DSiNPs as compared with SiNPs can be explained by the fact that the biopolymer shell of the polysaccharide provides a stronger adhesion of nanoparticles to the bacterial surface. Transmission electron microscopy (TEM) studies showed that the bacterial lipid shell was partially perforated after the combined treatment of DSiNPs and USI, which can be explained by the lysis of bacterial membrane due to the cavitation sensitized by the SiNPs. Furthermore, we have shown that 100% inhibition of E. coli bacterial colony growth is possible by coupling the treatments of DSiNPs and USI with an increased intensity of up to 3 W/cm2. The observed results reveal the application of SiNPs as promising antimicrobial agents.
The effect of severe plastic deformation, namely, high-pressure torsion (HPT) at different temperatures and ball milling (BM) at different time intervals, has been investigated by means of Mossbauer spectroscopy in Fe100-xMnx (x=4.1, 6.8, 9) alloys. Deformation affects the short-range clustering (SRC) in BCC lattice. Two processes occur: destruction of SRC by moving dislocations and enhancement of the SRC by migration of non-equilibrium defects. Destruction of SRC prevails during HPT at 80-293K; whereas enhancement of SRC dominates at 473-573K. BM starts enhancing the SRC formation at as low as 293K due to local heating at impacts. The efficiency of HPT in terms of enhancing SRC increases with increasing temperature. The authors suppose that at low temperatures, a significant fraction of vacancies are excluded from enhancing SRC because of formation of mobile bi- and tri-vacancies having low efficiency of enhancing SRC as compared to that of mono vacancies. Milling of BCC Fe100-xMnx alloys stabilises the BCC phase with respect to transition at subsequent isothermal annealing because of a high degree of work hardening and formation of composition inhomogeneity.
The condensation of 1-(ferrocenylalkyl)pyrazole-3-carbaldehydes with 4′-aminotetraphenylporphyrin, followed by reduction with NaBH(OAc) 3 in 1,2-dichloroethane, provides a convenient method for the synthesis of 5-{4-[({1-[1-(ferrocen-1-yl)alkyl]-5-methyl-1 H -pyrazol-3-yl}methyl)amino]phenyl}-10,15,20-triphenylporphyrins which exhibit pronounced cytotoxicity against Staphylococcus aureus under ultrasonic irradiation.
PURPOSE OF THE STUDYDevelop a method of treatment of prostatitis based on the use of a standard antibiotic, immunomodulatory therapy, and transrectal ultrasound physiotherapy.MATERIALS AND METHODSThe dynamics of the accumulation of the antibiotic was investigated in male rats. Sonication was performed immediately before the administration of the antibiotic and its accumulation in the process at 10, 20, 40, 60, 80, 100 min after dosing. The clinical study included 138 patients with chronic prostatitis. Patients of the experimental group, in addition to standard therapy, 10 sessions of transrectal ultrasound physical therapy was performed. The efficacy of treatment was assessed after 14 and 28 days after initiation.RESULTSand its discussion. Experiments on laboratory animals have shown that the highest concentration and the residence time of antibiotic in the prostate tissue is noted ultrasonic treatment in the period of maximum blood concentration of the test drug. The data obtained allow to determine that the ultrasonic treatment must be performed considering the pharmacokinetics of the antibiotic. In conducting clinical trials on day 14 of treatment and clinical manifestations of prostatitis bacterial microflora in prostatic secretions were no patients in both groups. In 15% of patients of the experimental group the number of leukocytes decreased to the normal range. After 28 days the amount of leukocytes was normal in 51% of patients in the control and 85% in the experimental group.CONCLUSIONIn animal experiments defined the optimal time interval separating the moment of injection of the antibiotic from the beginning of sonication. Clinical studies have shown that the transrectal ultrasound exposure during the period of maximum concentration of the antibiotic in the blood, improves patient outcomes by 33.8%.
Using bacterial model systems, it was shown that the addition of the soluble compound sodium salt of cobalt octacarboxyphthalocyanine (teraphtal) to a medium reduced the proportion of bacteria that survived in an ultrasonic field. It was hypothesized that in the bacterial environment teraphtal forms a solid phase that under exposure to an ultrasonic field destroys the structures that are adjacent to the nanocrystals due to local cavitation processes.
Luminescent porous silicon nanoparticles with mean size of about 100 nm were covered by biodegradable polymer (dextran) and were investigated as potential sensitizers for ultrasound-assisted therapy. Luminescent confocal microscopy revealed an efficient uptake of the nanoparticles by cancer cells in vitro. The nanoparticles were found to be almost nontoxic up to the concentration of 0.1 mg/mL and doses of 30 mg/kg as it was confirmed by in vitro and in vivo experiments, respectively. A strong suppression of the cancer cell proliferation was observed after a combined treatment by the nanoparticles and therapeutic ultrasound irradiation with frequencies of 1-3 MHz and intensities of 1-2 W/cm(2). The obtained results are discussed in view of potential applications of biocompatible and biodegradable silicon-based nanoparticles in sonodynamic therapy of cancer. (c) 2015 Elsevier Inc. All rights reserved.