Erzsébet Illés

Hydroxyl radical induced degradation of ibuprofen

Pulse radiolysis experiments were used to characterize the intermediates formed from ibuprofen during electron beam irradiation in a solution of 0.1mmoldm(-3). For end product characterization (60)Co γ-irradiation was used and the samples were evaluated either by taking their UV-vis spectra or by HPLC with UV or MS detection. The reactions of OH resulted in hydroxycyclohexadienyl type radical intermediates. The intermediates produced in further reactions hydroxylated the derivatives of ibuprofen as final products. The hydrated electron attacked the carboxyl group. Ibuprofen degradation is more efficient under oxidative conditions than under reductive conditions. The ecotoxicity of the solution was monitored by Daphnia magna standard microbiotest and Vibrio fischeri luminescent bacteria test. The toxic effect of the aerated ibuprofen solution first increased upon irradiation indicating a higher toxicity of the first degradation products, then decreased with increasing absorbed dose.

Chemical and Colloidal Stability of Carboxylated Core-Shell Magnetite Nanoparticles Designed for Biomedical Applications

Despite the large efforts to prepare super paramagnetic iron oxide nanoparticles (MNPs) for biomedical applications, the number of FDA or EMA approved formulations is few. It is not known commonly that the approved formulations in many instances have already been withdrawn or discontinued by the producers; at present, hardly any approved formulations are produced and marketed. Literature survey reveals that there is a lack for a commonly accepted physicochemical practice in designing and qualifying formulations before they enter in vitro and in vivo biological testing. Such a standard procedure would exclude inadequate formulations from clinical trials thus improving their outcome. Here we present a straightforward route to assess eligibility of carboxylated MNPs for biomedical tests applied for a series of our core-shell products, i.e., citric acid, gallic acid, poly(acrylic acid) and poly(acrylic acid-co-maleic acid) coated MNPs. The discussion is based on physicochemical studies (carboxylate adsorption/desorption, FTIR-ATR, iron dissolution, zeta potential, particle size, coagulation kinetics and magnetization measurements) and involves in vitro and in vivo tests. Our procedure can serve as an example to construct adequate physico-chemical selection strategies for preparation of other types of core-shell nanoparticles as well.

Water in contact with magnetite nanoparticles, as seen from experiments and computer simulations.

The adsorption of water vapor at the surface of magnetite nanoparticles has been investigated both by experimental and by computer simulation methods. The water vapor adsorption/desorption isotherm has been measured on freshly prepared magnetite nanocrystals of the size below 10 nm. The change of the isosteric heat of adsorption with the surface coverage has been determined from the temperature dependence of this isotherm using the isosteric method. The adsorption isotherm has also been determined by performing a set of grand canonical Monte Carlo simulations at 300 K. X-ray photoelectron spectroscopy results as well as the temperature and coverage dependence of the isosteric heat of adsorption clearly indicates that dissociative chemisorption of the water molecules in the first adsorption layer occurs at the bare magnetite surface, resulting in a high density of surface hydroxyl groups. This dissociative chemisorption is followed by a multilayer physisorption of water at higher pressures. Computer simulation results can reproduce excellently both the adsorption isotherm and the isosteric heat of adsorption beyond the first chemisorbed layer of water. Results of the computer simulations reveal that physisorbed water forms several well-distinguished molecular layers on the magnetite surface; however, these layers are not built up sequentially. Instead, the building up of several molecular layers occurs simultaneously. The adsorption of the water molecules in this range appears to be a nucleation-like process, resulting in a rather rough external surface of the adsorption layer.

Ketoprofen removal by O3 and O3/UV processes: Kinetics, transformation products and ecotoxicity

Ozonation (O3) and its combination with ultraviolet radiation (O3/UV) were used to decompose ketoprofen (KET). Depending on the initial KET concentration, fourteen to fifty times faster KET degradation was achieved using combined O3/UV method compared to simple ozonation. Using both methods, formation of four major aromatic transformation products were observed: 3-(1-hydroxyethyl)benzophenone, 3-(1-hydroperoxyethyl) benzophenone, 1-(3-benzoylphenyl) ethanone and 3-ethylbenzophenone. In the combined treatment the degradation was mainly due to the direct effect of UV light, however, towards the end of the treatment, O3 highly contributed to the mineralization of small carboxylic acids. High (~90%) mineralization degree was achieved using the O3/UV method. Toxicity tests performed using representatives of three trophic levels of the aquatic ecosystems (producers, consumers and decomposers) Pseudokirchneriella subcapitata green algae, Daphnia magna zooplanktons and Vibrio fischeri bacteria showed that under the used experimental conditions the transformation products have significantly higher toxicity towards all the test organisms, than KET itself. The bacteria and the zooplanktons showed higher tolerance to the formed products than algae. The measured toxicity correlates well with the concentration of the aromatic transformation products, therefore longer treatments than needed for complete degradation of KET are strongly suggested, in order to avoid possible impact of aromatic transformation products on the aquatic ecosystem.

Designed polyelectrolyte shell on magnetite nanocore for dilution-resistant biocompatible magnetic fluids

Magnetite nanoparticles (MNPs) coated with poly(acrylic acid-co-maleic acid) polyelectrolyte (PAM) have been prepared with the aim of improving colloidal stability of core-shell nanoparticles for biomedical applications and enhancing the durability of the coating shells. FTIR-ATR measurements reveal two types of interaction of PAM with MNPs: hydrogen bonding and inner-sphere metal-carboxylate complex formation. The mechanism of the latter is ligand exchange between uncharged -OH groups of the surface and -COO(-) anionic moieties of the polyelectrolyte as revealed by adsorption and electrokinetic experiments. The aqueous dispersion of PAM@MNP particles (magnetic fluids - MFs) tolerates physiological salt concentration at composition corresponding to the plateau of the high-affinity adsorption isotherm. The plateau is reached at small amount of added PAM and at low concentration of nonadsorbed PAM, making PAM highly efficient for coating MNPs. The adsorbed PAM layer is not desorbed during dilution. The performance of the PAM shell is superior to that of poly(acrylic acid) (PAA), often used in biocompatible MFs. This is explained by the different adsorption mechanisms; metal-carboxylate cannot form in the case of PAA. Molecular-level understanding of the protective shell formation on MNPs presented here improves fundamentally the colloidal techniques used in core-shell nanoparticle production for nanotechnology applications.

Magnetite Nanoparticles Stabilized Under Physiological Conditions for Biomedical Application

The biomedical application of water based magnetic fluids (MFs) is of great practical importance. Their colloidal stability under physiological conditions (blood pH ∼ 7.2–7.4 and salt concentration ∼0.15 M) and more in high magnetic field gradient is crucial. Magnetite or maghemite nanoparticles are used in general. In the present work, magnetite nanoparticles were stabilized with different compounds (citric acid (CA) and phosphate) and sodium oleate (NaO) as the most used surfactant in the stabilization of MFs. The adsorption and overcharging effect were quantified, and the enhancement in salt tolerance of stabilized systems was studied. Adsorption, electrophoretic mobility and dynamic light scattering (DLS) measurements were performed. The electrolyte tolerance was tested in coagulation kinetic measurements. Above the adsorption saturation, the nanoparticles are stabilized in a way of combined steric and electrostatic effects. The aim was to research these two important effects and demonstrate that none of them alone is enough. The phosphate was not able to stabilize the ferrofluid in spite of our expectation, but the other two additives proved to be effective stabilizing agents. The magnetite was well stabilized by the surface complexation of CA above pH ∼ 5, however, the salt tolerance of citrate stabilized MFs remained much below the concentration of physiological salt solution, and more the dissolution of magnetite nanocrystals was enhanced due to Fe-CA complexation in aqueous medium, which may cause problems in vivo. The oleate double layers were able to stabilize magnetite nanoparticles perfectly at pH ∼ 6 preventing particle aggregation effectively even in physiological salt solution.

Mechanism of in Situ Surface Polymerization of Gallic Acid in an Environmental-Inspired Preparation of Carboxylated Core–Shell Magnetite Nanoparticles

Magnetite nanoparticles (MNPs) with biocompatible coatings are good candidates for MRI (magnetic resonance imaging) contrasting, magnetic hyperthermia treatments, and drug delivery systems. The spontaneous surface induced polymerization of dissolved organic matter on environmental mineral particles inspired us to prepare carboxylated core-shell MNPs by using a ubiquitous polyphenolic precursor. Through the adsorption and in situ surface polymerization of gallic acid (GA), a polygallate (PGA) coating is formed on the nanoparticles (PGA@MNP) with possible antioxidant capacity. The present work explores the mechanism of polymerization with the help of potentiometric acid-base titration, dynamic light scattering (for particle size and zeta potential determination), UV-vis (UV-visible light spectroscopy), FTIR-ATR (Fourier-transformed infrared spectroscopy by attenuated total reflection), and XPS (X-ray photoelectron spectroscopy) techniques. We observed the formation of ester and ether linkages between gallate monomers both in solution and in the adsorbed state. Higher polymers were formed in the course of several weeks both on the surface of nanoparticles and in the dispersion medium. The ratio of the absorbances of PGA supernatants at 400 and 600 nm (i.e., the E4/E6 ratio commonly used to characterize the degree of polymerization of humic materials) was determined to be 4.3, similar to that of humic acids. Combined XPS, dynamic light scattering, and FTIR-ATR results revealed that, prior to polymerization, the GA monomers became oxidized to poly(carboxylic acid)s due to ring opening while Fe(3+) ions reduced to Fe(2+). Our published results on the colloidal and chemical stability of PGA@MNPs are referenced thoroughly in the present work. Detailed studies on biocompatibility, antioxidant property, and biomedical applicability of the particles will be published.

Hemocompatibility and Biomedical Potential of Poly(Gallic Acid) Coated Iron Oxide Nanoparticles for Theranostic Use

Polyacid covered core-shell iron oxide nanoparticles were designed for potential use in biomedicine with special attention to theranostics - magnetic resonance imaging (MRI), magnetic hyperthermia and magnetic drug targeting. The magnetite nanoparticles coated with a gallic acid shell polymerized in situ on the nanoparticle surface (PGA@MNPs) were tested for hemocompatibility in blood, sedimentation rate, blood smear and blood cell viability experiments and for antioxidant capacity in Jurkat cells in the presence of H2O2 as reactive oxygen species. No signs of interaction of the nanoparticles with whole blood cells were found. In addition, the PGA@MNPs reduced significantly the oxidative stress mediated by H2O2 supporting earlier findings of MTT tests, namely, the improvement of cell viability in their presence. The in vitro tests revealed that PGA@MNPs are not only biocompatible but also bioactive. Preliminary experiments revealed that the nanoparticles are especially efficient MRI and magnetic hyperthermia agents. The r2 relaxivity was found to be one of the highest among published values (387 mM-1s-1) and they possess a relatively significant specific absorption rate (SAR) value of 11 W/g magnetite.

Polyelectrolyte coating on superparamagnetic iron oxide nanoparticles as interface between magnetic core and biorelevant media

Nanoparticles do not exist in thermodynamical equilibrium because of high surface free energy, thus they have only kinetic stability. Spontaneous changes can be delayed by designed surface coating. In biomedical applications, superparamagnetic iron oxide nanoparticles (SPIONs) require an optimized coating in order to fulfil the expectation of medicine regulatory agencies and ultimately that of biocompatibility. In this work, we show the high surface reactivity of naked SPIONs due to ≡Fe–OH sites, which can react with H+/OH− to form pH- and ionic strength-dependent charges. We explain the post-coating of naked SPIONs with organic polyacids via multi-site complex bonds formed spontaneously. The excess polyacids can be removed from the medium. The free COOH groups in coating are prone to react with active biomolecules like proteins. Charging and pH- and salt-dependent behaviour of carboxylated SPIONs were characterized quantitatively. The interrelation between the coating quality and colloidal stability measured under biorelevant conditions is discussed. Our coagulation kinetics results allow us to predict colloidal stability both on storage and in use; however, a simpler method would be required to test SPION preparations. Haemocompatibility tests (smears) support our qualification for good and bad SPION manufacturing; the latter ‘promises’ fatal outcome in vivo.

The effect of hydroxyl moieties and their oxosubstitution on bile acid association studied in floating monolayers

Bile salt aggregates are promising candidates for drug delivery vehicles due to their unique fat-solubilizing ability. However, the toxicity of bile salts increases with improving fat-solubilizing capability and so an optimal combination of efficient solubilization and low toxicity is necessary. To improve hydrophilicity (and decrease toxicity), we substituted hydroxyl groups of several natural bile acid (BA) molecules for oxogroups and studied their intrinsic molecular association behavior. Here we present the comparative Langmuir trough study of the two-dimensional (2D) association behavior of eight natural BAs and four oxoderivatives (traditionally called keto-derivatives) floated on an aqueous subphase. The series of BAs and derivatives showed systematic changes in the shape of the compression isotherms. Two types of association could be distinguished: the first transition was assigned to the formation of dimers through H-bonding and the second to the hydrophobic aggregation of BA dimers. Hydrophobic association of BA molecules in the films is linked to the ability of forming H-bonded dimers. Both H-bond formation and hydrophobic association weakened with increasing number of hydroxyl groups, decreasing distance between hydroxyl groups, and increasing oxosubstitution. The results also show that the Langmuir trough method is extremely useful in selecting appropriate BA molecules to design drug delivery systems.