Single-walled carbon nanotubes loaded hydroxyapatite-alginate beads with enhanced mechanical properties and sustained drug release ability.

Single-walled carbon nanotubes (SWCNTs) containing biomaterial with enhanced mechanical properties for the potential orthopedic application were synthesized and investigated. X-ray diffraction and X-ray fluorescence analysis were indications of the formation of calcium-deficient (Ca/P = 1.65) hydroxyapatite (HA) with a small carbonate content under influence of microwave irradiation. The investigated mechanical properties (maximal relative deformation, compressive strength and Young's modulus) of SWCNT loaded HA-alginate composites confirm their dependence on SWCNTs content. The compressive strength of HA-alginate-SWCNT and the HA-alginate control (202 and 159 MPa, respectively) lies within the values characteristic for the cortical bone. The addition of 0.5% SWCNT, in relation to the content of HA, increases the Young's modulus of the HA-alginate-SWCNT (645 MPa) compared to the SWCNT-free HA-alginate sample (563 MPa), and enhances the material shape stability in simulated physiological conditions. Structural modeling of HA-alginate-SWCNT system showed, that physical adsorption of SWCNT into HA-alginate occurs by forming triple complexes stabilized by solvophobic/van der Waals interactions and H-bonds. The high-performance liquid chromatography demonstrated the influence of SWCNTs on the sustained anaesthesinum drug (used as a model drug) release (456 h against 408 h for SWCNT-free sample). Cell culture assay confirmed biocompatibility and stimulation of osteoblast proliferation of 0.05% and 0.5% SWCNT-containing composites during a 3-day cultivation. All these facts may suggest the potential possibility of using the SWCNT-containing materials, based on HA and alginate, for bone tissue engineering.

Synthesis, characterization, in vitro biocompatibility and antibacterial properties study of nanocomposite materials based on hydroxyapatite-biphasic ZnO micro- and nanoparticles embedded in Alginate matrix.

The paper presents the results of studies of biocompatibility and antibacterial properties of multiphase nanocomposite materials based on HA-Alg-ZnO (hydroxyapatite­sodium alginate-biphasic zinc oxide) and HA-ZnO (hydroxyapatite­zinc oxide), which were synthesized from the analytically pure calcium nitrate tetrahydrate, ammonium hydrophosphate, hydrous ammonia, zinc nitrate hexahydrate and calcium chloride. The samples' antimicrobial activity assessment was carried out on Gram-negative (E. coli, P. aeruginosa) and Gram-positive bacteria (S. aureus and S. epidermidis) test cultures by the co-incubation and modified "agar diffusion" methods. The murine fibroblast cells were used for the biocompatibility tests and cytotoxicity evaluation. It was shown that synthesized nanocomposite material has a multiphase nanoscale architecture, where ZnO nanocrystals are represented by two lattices: cubic and hexagonal. The possible explanation of ZnO nanocrystals' phase transition is given. At the same time, a partial replacement of Ca2+ ions by Zn2+ ions in the HA lattice possibly occurs due to processing of composite by US radiation. The replacement was evidenced by the non-stoichiometric Ca/P ratio < 2.16, OPO lines' shifting on FTIR spectrum and TEM analysis. The studied composite demonstrate a pronounced antibacterial activity due to the incorporation of ZnO particles into sodium alginate and moistened powder of hydroxyapatite. Both forms of HA-ZnO (suspension) and HA-Alg-ZnO (beads) are biocompatible. An interpretation of the process of Zn ions' embedding into hydroxyapatite and alginate matrix is given, as well as their influence on the biomimetic composite properties is discussed in details. STATEMENT OF SIGNIFICANCE: A number of studies have shown that Zn effectively inhibits the growth and development of bacteria and yeast fungi. Zinc plays an important role in the creation of new antimicrobial agents, and zinc-doped hydroxyapatite will find further application in biomedicine. In this regard, the phase states of zinc oxide, as well as the processes of calcium replacement by zinc in calcium apatite and in alginate should be explored fully. Nowadays we have lack of information and the study's results about those interactions. The present study provides data of the multiphase morphology, antimicrobial activity, biocompatibility and cytotoxicity of the biomimetic nanostructured composite materials, such as sodium alginate/hydroxyapatite/ZnO based granules and hydroxyapatite/ZnO based hydrogel, and the establishing Zn ions' behavior patterns with another composite components.

C60 fullerene loaded hydroxyapatite-chitosan beads as a promising system for prolonged drug release.

Bioactive composite material in the form of beads, based on natural polysaccharide Chitosan (CS), hydroxyapatite (HA), and C60 fullerene (C60), was synthesized under influence of microwave irradiation (MW). The bead is a 3D matrix consisting of CS macromolecules cross-linked with sodium tripolyphosphate with HA and C60 particles immobilized in its structure. XRD and FTIR data confirmed the formation of calcium deficient carbonate substituted HA with needle-shaped nanocrystallites of about 80 nm. MW does not influence CS structure. C60 enhances the beads shape stability. HPLC studies suggest the (up to 18 days) prolonged release of hydrophobic Anaesthesinum from C60-containing composites. Changing the C60 content allows adjusting the drug release time. The presence of CS and C60 provides the Anaestesinum release profile, according to the calculated correlation coefficient (r = 0.99), close to the zero order kinetic release profile. The inhibition zone test (ZOI) shows the antimicrobial activity of the composites containing 0.004 mg/ml C60 against S. aureus ATCC 25923 and E. coli ATCC 25922 (ZOI 16 ±â€¯1 and 10 ±â€¯2 mm, respectively). Cell viability test indicates no toxicity of 0.3 and 0.15 mg/ml C60-containing composites.

Composite material based on hydroxyapatite and multi-walled carbon nanotubes filled by iron: Preparation, properties and drug release ability.

The novel bioactive composite material based on hydroxyapatite and multi-walled carbon nanotubes filled by iron was synthesized by the "wet chemistry" method and characterized in detail by various experimental techniques including the X-ray diffraction, Fourier transform infrared and energy-dispersive X-ray fluorescence spectroscopy, thermogravimetric and differential thermal analysis. The swelling behaviour was quantified by measuring the changes in sample weight as a function of sample immersion time in a phosphate buffered saline (PBS). Bioactivity test was carried out by soaking the samples in PBS. The material composition influence on the model drug release was studied using the high-performance liquid chromatography method. Finally, the mechanical properties (maximal relative deformation, strength and Young's modulus) of the samples under loading were investigated too. The findings clear demonstrate the possibility of application of the created composite material in bioengineering of bone tissue to fill bone defects of various geometries with the function of prolonged release of the drug. It is assumed that this composite material can be used in 3D modeling of areas of bone tissue that have to bear a mechanical load.

Structural features of hydroxyapatite and carbonated apatite formed under the influence of ultrasound and microwave radiation and their effect on the bioactivity of the nanomaterials.

The samples of hydroxyapatite and carbonate substituted hydroxyapatite (CHA) were obtained under the influence of physical factors, namely ultrasound (US) and microwave (MW) radiations. The results of Fourier transform infrared spectroscopy and X-ray diffraction analysis have proved the formation of the calcium deficient hydroxyapatite and B-type CHA with the Ca/P ratio in the ranges 1.62-1.87. In vitro studies have showed the increased bioactivity of the samples, synthesized under the influence of physical factors as compared to the standard ones. The samples of both groups, synthesized under the influence of 600 W MW, have shown the greatest stability in biological environment. In vivo tests confirm that obtained under US and MW radiations hydroxyapatite-based biomaterials are biocompatible, non-toxic and exhibit osteoconductive properties. The usage of US and MW radiations can significantly shorten the time (up to 5-20 min) of obtaining of calcium deficient hydroxyapatite and B-type CHA in nanopowder form, close in structure and composition to the biological hydroxyapatite.

Controllability of brushite structural parameters using an applied magnetic field.

The paper studies the influence of low intensity static magnetic field on brushite structural and microstructural parameters using the X-ray diffraction and the transmission electron microscopy. This effect was shown to have various influences on DCPD (Dicalcium Phosphate Dihydrate) structure depending on a magnetic field configuration or time of synthesis, which allows achieving controllability of the main properties of an obtained material. The influence of the magnetic field leads mostly to the decrease of crystallite sizes with no impact on the crystal lattice parameters. In (0 2 0) and (1 5 0) planes the growth of crystallite sizes is observed after 2 and 3 days of crystallization, respectively. The analysis of different contributions to peak broadening in [0 b 0] direction showed a similar trend for the crystallite sizes with the lower lattice microstrains after 2 days of synthesis. The effect similar to the preferred orientation was observed and classified with the Harris method.

[Interaction of DNA nucleotide bases with anticancer drug ThioTEPA: molecular docking and quantum-mechanical analysis].

Using modern methods of molecular docking, quantum chemistry and quantum theory of atoms in molecules the interaction of anticancer drug ThioTEPA with isolated nucleotide bases and deoxyribonucleosidemonophosphates of DNA has been studied. Physical properties and some trends of binding have been established for the complexes of "nucleotide base + ThioTEPA" and "deoxyribonucleosidemonophosphate + ThioTEPA" types. It has been shown that strong hydrogen bonds of NH...N type are the key factor responsible for high selectivity of binding of ThioTEPA to the guanine-containing units of the DNA.

Silver-doped hydroxyapatite coatings formed on Ti-6Al-4V substrates and their characterization.

Coatings with antibacterial components for medical implants are recommended to reduce the risk of bacterial infections. Therefore hydroxyapatite (HA) coatings with addition of chitosan (CS) and silver (Ag) are proposed in this work in an attempt to resolve this problem. Ti-6Al-4V substrates were modified by a chitosan film to study the influence of surface modification on the formation of the HA-Ag and HA-CS-Ag coatings. Using a thermal substrate method, HA and HA-CS coatings doped with Ag(+) were prepared at low substrate temperatures (90°C). Coated surfaces were examined using X-ray diffraction and scanning electron microscopy. The amount of silver in the deposited coatings was analyzed by atomic absorption spectroscopy. From this study it is concluded that the substrate surface modified by a chitosan film promotes the coating formation and increases the antibacterial activity of produced coatings against a strain of Escherichia coli. The adhesion of E. coli (ATCC 25922) to sheep erythrocytes was decreased by 14% as compared with the reference samples without Ag. It could be explained by the inhibition of bacterial adhesins by Ag(+) ions released. The combined action of silver ions and chitosan resulted in a 21% decrease in adhesive index.

N-isopropylacrylamide-based fine-dispersed thermosensitive ferrogels obtained via in-situ technique.

Thermosensitive hydrogels with magnetic properties (ferrogels) are very promising for medical application, first of all, for the design of targeted delivery systems with controlled release of drugs and for magnetic hyperthermia and chemotherapy treatment of cancer. These magnetic hydrogels could be obtained using diverse techniques: ex- and in-situ syntheses. The present work is devoted to the study of magnetite (Fe(3)O(4)) formation inside the nanoreactors of (co)polymeric hydrogels. Polymeric templates (hydrogel films and fine-dispersed hydrogels) used for obtaining ferrogels were based on acrylic monomers: thermosensitive N-isopropylacrylamide, and hydrophilic acrylamide. Covalent cross-linking was accomplished using bifunctional monomer N,N'-methylenebisacrylamide. Influence of hydrophilic-lipophilic balance of polymeric templates and concentration of iron cations on the magnetite formation were investigated along with the development of ferrogel preparation technique. Cytotoxicity, physical and chemical properties of obtained magnetic hydrogels have been studied in this work.

A study of brushite crystallization from calcium-phosphate solution in the presence of magnesium under the action of a low magnetic field.

The paper discusses the crystallization of dicalcium phosphate dehydrate (DCPD) with subsequent transformation to nanocrystalline hydroxyapatite (НA) under the permanent magnetic field in the presence of magnesium. It was found that the presence of magnesium in the initial solution in concentrations of 0.01-0.03g/l decreased the crystallinity of calcium-phosphates. The precipitation of DCPD under the magnetic field of 0.3T was carried out in proximity of the north and south magnetic poles. The differences in the particle morphology and structure of precipitates with the same phase composition (DCPD) were observed in the neighborhood of the north and the south pole. Lattice parameters of DCPD precipitates obtained biomimetically near opposite magnet poles were calculated using XRD results. It was found that the increased crystallization time (more than 3days) leads to a complete attenuation of DCPD peaks, whereas НА peaks are still present.

[Measurement of trace elements in blood serum by atomic absorption spectroscopy with electrothermal atomization]. / Opredelenie soderzhaniia mikroélementov v syvorotke krovi metodom atomno-absorbtsionnoi spektroskopii s élektrotermicheskoi atomizatsiei.

Describes a method for measuring trace elements Cr, Mn, Co, Fe, Cu, Zn, and Mo in the blood serum using non-flame atomization (KAC 120.1 complex). Optimal conditions for preparing the samples were defined, temperature regimens for analysis of each element selected, and original software permitting automated assays created. The method permits analysis making use of the minimal samples: 0.1 ml per 10 parallel measurements, which is 100 times less than needed for atomic absorption spectroscopy with flame atomization of liquid samples. Metrological characteristics of the method are assessed.

[Mass spectrometric and quantum chemical study of dimeric associates of nucleosides]. / Mass-spektrometricheskoe i kvantovokhimicheskoe issledovanie dimernykh assotsiatov nukleozidov.

Deoxyribonucleosides H-bonded pairs were investigated using fast atom bombardment mass spectrometry and MNDO/H quantum chemistry method. It was shown that "rare" (enol or imin) forms of the nitrogen bases could form pairs with energy comparable with "canonical" base pair energy. It was shown that pair stability rows, which are measured using different experimental techniques, were in conformity each with other.

[Use of time-of-flight mass spectrometry with ionization division fragments of californium-252 for studying the mechanisms of action of drugs on DNA and its components]. / Primenenie vremia proletnoi mass-spektrometrii s ionizatsiei oskolkami deleniia kaliforniia-252 k izucheniiu mekhanizmov deistviia lekarstvennykh preparatov na DNK i ee komponenty.

Using soft-ionization mass spectrometry (252-Cf particle desorption mass spectrometry, PDMS) a minor adduct of anticancer drug prospidine and deoxyguanosine-5-phosphate (pdG) has been found. It has been shown experimentally that PDMS is very useful for study of biological mixtures as well as mechanisms of interactions between drugs and biomolecules.

Study of anticancer drug interaction with DNA by means of particle-induced desorption mass spectrometry: prospydine and deoxyguanosine-5'-monophosphate.

Using 252CF particle desorption mass spectrometry, the interaction between an antitumour drug prospydine (Pro) and deoxyguanosine-5'-monophosphate (pdG) has been studied. The adduct which corresponds to a peak at m/z 524.5 and which occurs as a result of the particular degradation of Pro during its alkylating of pdG has been found.

[Study of the interaction of triethylenethiophosphamide with nucleotides by mass spectrometry with ionization by fission fragments of californium-252]. / Izuchenie vzaimodeistviia triétilentiofosfamida s nukleotidami metodom mass-spektrometrii s ionizatsiei oskolkami deleniia kaliforniia-252.

Study of interaction of the antitumor alkylating drug triethylenethiophosphoramide (thioTEPA) with nucleotides (dGMP and dCMP) suggests highly perspective employment of 252-Cf fission fragment induced desorption mass spectrometry (252-Cf PDMS) in biochemical pharmacology. Using the 252-Cf PDMS the molecular masses of the unstable, unvolatile, high-molecular substances of biological origin and the chemical adducts or complexes with drugs can be used to establish some structural-functional parameters of the above mentioned biomolecules and their derivatives in microvolumes of the incubation medium. The resulting data may be used for modelling chemotherapeutic processes of "drug-biomolecule-target" type. Using 252-Cf PDMS the complexes (dGMP (thioTEPA) n), n = 1, 2, 3 and (dCMP (thioTEPA) n), n = 1, were obtained. Some quantitative parameters and stability of these complexes were studied. Binding of dGMP with drug in the presence of dCMP was shown preferential. The data are compatible with the predictions concerning the mechanism of the antitumor property of the thioTEPA which can be manifested in the impairment structure of DNA of the malignant cells.

Direct observation of the alkylation products of deoxyguanosine and DNA by fast atom bombardment mass spectrometry.

By the methods of fast atom bombardment (FAB) mass spectrometry, thin-layer chromatography and ultraviolet absorption spectroscopy adducts have been studied which are formed by an antitumour alkylating drug thiotepa both in a model system, containing only deoxyguanosine (dGuo), and in DNA. Analysis of the model reaction mixture (dGuo + thiotepa) by FAB mass spectrometry permitted observation of adducts dGuo thiotepa, 2dGuo thiotepa, and also the products of their further modification in solution, which occurs by hydrolysis of the glycosidic bond and also by opening of the imidazole ring. In the case of DNA FAB mass spectrometry made it possible to characterize adducts of thiotepa with guanosine (Gua) and adenosine (Ade) without their preliminary purification. The site of alkylation of Gua in both dGuo and DNA is N7, and that of Ade in DNA is N3. The application of the results to the study of the molecular mechanism of the antitumour action of thiotepa is discussed.

Experimental and theoretical study of energetics of complex formation between nucleic acid bases and the bases with amide group.

A number of nucleic acid base pairs and complexes between the bases and the amide group of acrylamide have been studied experimentally by using mass spectrometry and theoretically by the method of atom-atom potential function calculations. It has been found from temperature dependencies of peak intensities in mass spectra of m2.2.9(3) Gua.m1Ura, m9 Ade.m1Cyt, m2.2.9(3) Gua.m1Gua.m1Cyt pairs that enthalpy values, delta H, of the complex formation are equal to 14.2 +/- 1.1, 13.5 +/- 1.3 and 16.4 +/- 1.4 kcal/M, respectively, and those of acrylamide with m1.3(2) Ura and m1Thy corresponds to 9.7 +/- 1.0 and 6.8 +/- 0.6 kcal/M. There is a good agreement of the experimental data with calculations when taking into account both the amino-oxo and the amino-hydroxy tautomeric forms of guanine. A combined use of the data allows us to determine the energy, the modes of interaction and the structure of the complexes. The results are discussed in connection with the modelling of molecular structure of biopolymers by the method of classical potential functions, protein-nucleic acids recognition and fidelity of nucleic acids biosynthesis.

Associate hydrations and energies of nucleotide bases as revealed by low-temperature field ionization mass-spectrometric data.

The formation of water clusters, polyhydrates of nucleotide bases and their associates during simultaneous condensation of water and base molecules in vacuo onto a surface of a needle emitter cooled to 170 K was studied by field ionization mass spectrometry. It was found that different emitter temperatures are characterized by a specific distribution of intensities of cluster currents, depending on the number of water molecules in clusters. These distributions correlate with structural peculiarities and the relative energetics of formation of water clusters, polyhydrates of nucleotide bases and their associates at low temperature. The features observed in mass spectra for clusters m9Ade (H2O)5, m1Ura (H2O)4 and m9Ade m1Ura (H2O)2 are treated as a result of formation of energetically favorable structures stabilized by H-bonded bridges of water molecules. The relative association constants and formation enthalpies of the noncomplementary pairs Ade Cyt, Gua Ura and the associates which model the aminoacid-base complexes m1Ura Gln and m1.3(2)Thy Gln were determined from the temperature dependencies of the intensities of mass spectra peaks in the range 290-320 K.