Effective intracellular release of ibuprofen triggered by thermosensitive magnetic nanocarriers.

Stimuli-responsive nanocarriers are being widely applied in the development of new strategies for the diagnosis and treatment of diseases. An inherent difficulty in general drug therapy is the lack of precision with respect to a specific pathological site, which can lead to toxicity, excessive drug consumption, or premature degradation. In this work, the controlled drug delivery is achieved by using magnetite nanoparticles coated with mesoporous silica with core-shell structure (MMS) and grafted with the thermoresponsive polymer poly [N-isopropylacrylamide-co-3-(trimethoxysilyl)propyl methacrylate] (MMS-P). The efficiency of MMS-P as a temperature-controlled drug delivery system was evaluated by in vitro release experiments using ibuprofen (IBU) in various mammalian cell models. Further, the effects of IBU as a photoprotectant in cells exposed to photodynamic therapy (PDT) in a carbaryl-induced neurodegenerative model were evaluated. The results showed that MMS-P nanocarriers do not exhibit cytotoxicity in HepG2 cells at high doses such as 7600 µg mL-1. Pre-incubation of MMS-P charged with IBU showed no effect on the PDT in N2A cells; however, it produced a further decrease in the viability of HepG2 cells, leading to a reduction to PDT resistance. On the other hand, a cytoprotective effect against carbaryl toxicity in N2A cells was observed in IBU administrated by MMS-P, which confirms the effective intracellular IBU uptake by means of MMS-P. These results encourage the potential application of MMS-P as a drug delivery system and confirm the effect of IBU as a cytoprotective agent in a neurodegenerative model.

Removal of As(III) via adsorption and photocatalytic oxidation with magnetic Fe-Cu nanocomposites.

Magnetic Fe-Cu nanocomposites with high adsorption capacity and photocatalytic properties were prepared via the precursor method using soluble substances isolated from urban biowaste (BBS) as carbon sources and different temperatures of the pyrolysis treatment (400, 600, and 800 °C). BBS is used as complexing agent for the Fe3+ and Cu2+ ions in the precursors. The as-prepared magnetic materials were tested in As(III) removal processes from water. Dark experiments performed with the materials obtained at 400 and 600 °C showed excellent adsorption capacities achieving a significant uptake of 911 and 840 mg g-1 for As(III), respectively. Experiments conducted under steady-state irradiation showed a reduction of 50-71% in As(III) levels evidencing the meaningful photocatalytic capacity of Fe-Cu nanocomposites. The best photocatalytic performance was obtained for the nanocomposite synthesized at the highest pyrolysis temperature, in line with the reported trend of HO· radicals production. Transient absorption spectroscopy experiments revealed the occurrence of an alternative oxidation pathway involving the valence band holes and yielded relevant kinetic information related to the early stages of the As(III) photooxidation. The higher absorption of the electron-hole pairs observed for the samples treated at lower temperature means that controlling the pyrolysis temperature during the synthesis of the Fe-Cu nanocomposites allows tuning the photocatalyst activity for oxidation of substrates via valence band holes, or via HO· radicals.

Carbamazepine Degradation Mediated by Light in the Presence of Humic Substances-Coated Magnetite Nanoparticles.

The use of iron-based nanomaterials for environmental remediation processes has recently received considerable attention. Here, we employed core-shell magnetite-humic acids nanoparticles as a heterogeneous photosensitizer and iron source in photo-Fenton reaction for the degradation of the psychiatric drug carbamazepine (CBZ). CBZ showed low photodegradation rates in the presence of the magnetic nanoparticles, whereas the addition of hydrogen peroxide at pH = 3 to the system drastically increased the abatement of the contaminant. The measured Fe2+ and Fe3+ profiles point to the generation of Fe3+ at the surface of the nanoparticles, indicating a heterogeneous oxidation of the contaminant mediated by hydroxyl radicals. Products with a higher transformation degree were observed in the photo-Fenton procedure and support the attack of the HO• radical on the CBZ molecule. Promising results encourage the use of the nanoparticles as efficient iron sources with enhanced magnet-sensitive properties, suitable for applications in photo-Fenton treatments for the purification of wastewater.

Synthesis and in vitro testing of thermoresponsive polymer-grafted core-shell magnetic mesoporous silica nanoparticles for efficient controlled and targeted drug delivery.

In this work, thermoresponsive polymer grafted magnetic mesoporous silica nanoparticles were prepared, fully characterized and tested as controlled drug delivery systems. For this purpose, iron oxide nanoparticles coated with mesoporous silica shell were grafted with poly(N-isopropylacrylamide-co-3-(methacryloxypropyl)trimethoxysilane) (PNIPAM-co-MPS). The grafting and polymerization on the as-prepared nanoparticles were performed in one-step procedure. Using this methodology, the polymer was successfully grafted mainly onto the silica surface, leaving the mesopores empty for the drug loading. The prepared hybrid nanoparticles (MMSNP-PNIPAM-co-MPS) showed high magnetization saturation (19.5 emu g-1) and high specific surface area (505 m2 g-1) and pore volume (0.29 cm3 g-1). Ibuprofen was used as a model drug to test the performance of the hybrid particles as thermosensitive drug delivery systems. For this, in vitro drug delivery tests were conducted below (25 °C) and above (40 °C) the lower critical solution temperature (LCST) of the polymer (PNIPAM-co-MPS). Considerable difference (80%) in the ibuprofen release at these two temperatures and a fast and complete release of the drug at 40 °C was observed. These results suggest that the thermoresponsive copolymer acts as a gatekeeper for the temperature-controlled release of the drug loaded inside the mesopores. Therefore, MMSNP-PNIPAM-co-MPS are promising magnetic and thermoresponsive nanocarriers for targeted delivery of therapeutic substances.

From biowaste to magnet-responsive materials for water remediation from polycyclic aromatic hydrocarbons.

Composted urban biowaste-derived substances (BBS-GC) are used as carbon sources for the preparation of carbon-coated magnet-sensitive nanoparticles obtained via co-precipitation method and the subsequent thermal treatment at 550 °C under nitrogen atmosphere. A multitechnique approach has been applied to investigate the morphology, magnetic properties, phase composition, thermal stability of the obtained magnet-sensitive materials. In particular, pyrolysis-induced modifications affecting the BBS-GC/carbon shell were highlighted. The adsorption capacity of such bio-derivative magnetic materials for the removal of hydrophobic contaminants such as polycyclic aromatic hydrocarbons was evaluated in order to verify their potential application in wastewater remediation process. The promising results suggest their use as a new generation of magnet-responsive easily-recoverable adsorbents for water purification treatments.

Sustainable magnet-responsive nanomaterials for the removal of arsenic from contaminated water.

In this study, chitosan and bio-based substances (BBS) obtained from composted biowaste were used as stabilizers for the synthesis of magnet-sensitive nanoparticles (NPs) via coprecipitation method. A pyrolysis treatment was carried out on both biopolymers at 550°C, and their consequent conversion into a carbon matrix was followed by means of different physicochemical characterization techniques (mainly FTIR spectroscopy and XRD), whereas magnetic properties were evaluated by magnetization curves. The prepared materials were tested in water remediation processes from arsenic (As) species (both inorganic and organic forms). These tests, explained by means of the most common adsorption models, evidenced that the best performances were reached by both materials obtained after pyrolysis treatments, pointing out the promising application of such magnet-sensitive materials as easy-recoverable tools for water purification treatments.

Soybean peroxidase immobilized onto silica-coated superparamagnetic iron oxide nanoparticles: Effect of silica layer on the enzymatic activity.

Peroxidase immobilization onto magnetic supports is considered an innovative strategy for the development of technologies that involves enzymes in wastewater treatment. In this work, magnetic biocatalysts were prepared by immobilization of soybean peroxidase (SBP) onto different silica-coated superparamagnetic iron oxide nanoparticles. The obtained magnetic biocatalysts were tested for the degradation of malachite green (MG), a pollutant often found in industrial wastewaters and with significant drawbacks for the human and environmental health. A deep physicochemical characterization of the materials was performed by means of X-ray diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), High Resolution-Transmission Electron Microscope (HR-TEM) and magnetization measurements among others techniques. Results showed high immobilization yield of SBP onto nanomaterials with excellent properties for magnetic recoverability. A partial loss of activity with respect to free SBP was observed, compatible with the modification of the conformational structure of the enzyme after immobilization. The structural modification depended on the amount (and thickness) of silica present in the hybrid materials and the activity yield of 43% was obtained for the best biocatalyst. Thermal stability and reusability capacity were also evaluated.

Photodegradation routes of the herbicide bromoxynil in solution and sorbed on silica nanoparticles.

Some organic contaminants dissolved in natural waters tend to adsorb on suspended particles and sediments. In order to mimic the photodegradation routes in natural waters of bromoxynil (BXN) adsorbed on silica, we here prepare and characterize silica nanoparticles modified with BXN (NP-BXN). We measure the direct photolysis quantum yield of aqueous BXN at 307 nm (0.064 ± 0.001) and detect the formation of bromide ions as a reaction product. Under similar conditions the photolysis quantum yield of BXN bonded to NP-BXN is much lower (0.0021 ± 0.0004) and does not lead to formation of bromide ions. The rate constant of the reaction of NP-BXN with the excited triplet states of riboflavin, a molecule employed as a proxy of chromophore dissolved organic matter (DOM) was measured in laser flash-photolysis experiments. The rate constants for the overall (kt) and chemical interaction (kr) of singlet oxygen with NP-BXN were also measured. Kinetic computer simulations show that the relevance of the direct and indirect (through reactions with reactive species generated in photoinduced processes) photodegradation routes of BXN is very much affected by sorption on silica. Immobilization of the herbicide on the particles, on one hand, affects the photolysis mechanism and lowers its photolysis quantum yield. On the other hand, the results obtained in aqueous suspensions indicate that immobilization also lowers the rate of collisional encounter, which affects the quenching rate constants of excited triplet states and singlet oxygen with the herbicide.

Photochemical fate of a mixture of emerging pollutants in the presence of humic substances.

The photodegradation of a mixture of the emerging pollutants (EPs) clofibric acid, amoxicillin, acetamiprid, acetaminophen, carbamazepine, and caffeine was studied under irradiation with a xenon lamp. The quantum efficiencies of the EPs were determined when irradiated individually. Experiments with the mixture of the EPs showed that indirect photoprocesses attributable to interaction between EPs can either enhance the photodegradation rate by photosensitization or decrease it by quenching processes. The addition of humic substances (HS) to the solutions resulted in an increase of indirect photoprocesses with higher effects on acetaminophen and carbamazepine; this was more remarkable when a filter was used to cut off radiation in the range 280-295 nm. Experiments carried out with chemical probes indicated that the triplet excited states of HS play a major role in the photosensitization process, although the contribution of other species cannot be completely ruled out. Additionally, V. fischeri toxicity tests showed a synergistic effect produced by the mixture of EPs before irradiation. Photodegradation resulted in an enhanced toxicity of the solution at the initial steps of the process, which was associated both with synergistic effects and with the formation of toxic photodegradation by-products of clofibric acid.

The role of humic acid aggregation on the kinetics of photosensitized singlet oxygen production and decay.

The effect of humic acid (HA) aggregate formation on the photosensitized generation and subsequent quenching of singlet molecular oxygen O(2)(a(1)Δ(g)) was investigated. Time-resolved O(2)(a(1)Δ(g)) phosphorescence traces were obtained from (a) bulk samples of HA dispersions and (b) microscope-based experiments performed upon irradiation of a single HA aggregate. In the bulk experiments, the dependence of the O(2)(a(1)Δ(g)) lifetime on the HA concentration yields a critical concentration for the formation of micrometric HA aggregates of 0.58 g L(-1). This value is consistent with that obtained using pyrene as a fluorescent probe (0.38 g L(-1)). Microscope-based experiments were also performed with HA samples containing added singlet oxygen sensitizers; either the hydrophobic meso-tetraphenylporphyrin (TPP) or the hydrophilic 5,10,15,20-tetrakis(N-methyl-4-pyridyl)-21H,23H-porphine (TMPyP). Singlet oxygen phosphorescence could only be detected upon irradiation of TMPyP, a molecule which localizes on the exterior part of the HA aggregates. The inability to detect O(2)(a(1)Δ(g)) phosphorescence from HA samples containing TPP is consistent with the model that the O(2)(a(1)Δ(g)) produced in the interior of the aggregate was completely quenched by the high local concentration of HA reactive groups in this environment.

Nitration of nitrobenzene in Fenton's processes.

Previous studies of nitrobenzene (NB) degradation by Fenton and photo-Fenton technologies have demonstrated the formation and accumulation of 1,3-dinitrobenzene (1,3-DNB) as a highly toxic reaction intermediate. In the present study, we analyze the conditions that favor 1,3-DNB formation during NB degradation by Fe(2+)/H(2)O(2), Fe(3+)/H(2)O(2), UV/Fe(3+)/H(2)O(2) or UV/H(2)O(2) processes. Nitration yields in Fenton, Fenton-like and photo-Fenton techniques were much higher than those observed in UV/H(2)O(2) systems. Besides, several tests showed that 1,3-DNB formation increases with the initial iron concentration and decreases as the initial H(2)O(2) concentration increases. In order to asses the key species involved in NB nitration mechanism, additional experiments were performed in the presence of NO(2)(-)or NO(3)(-). In dark systems, 1,3-DNB yield significantly increased with increasing [NO(2)(-)]_(0), while it was not affected by the presence of NO(3)(-). In contrast, 1,3-DNB yields were higher and more strongly affected by the additive concentration in UV/NO(3)(-) systems than in UV/HNO(2)/NO(2)(-) systems. Dark experiments performed at pH 1.5 in excess of HNO(2) along with UV/NO(3)(-) tests conducted in the presence of 2-propanol show that hydroxyl radicals play an important role in NB nitration since NB molecule does not react with the nitrating agents ONOOH, .NO or .NO(2). The results indicate that, in the experimental domain tested, the prevailing NB nitration pathway involves the reaction between the .OH-NB adduct and .NO(2) radicals.

Intermediate distributions and primary yields of phenolic products in nitrobenzene degradation by Fenton's reagent.

Nitrobenzene thermal degradation was investigated using the Fenton reagent in different experimental conditions. Reaction products were analyzed by HPLC, GC-MS, LC-MS and IC. The products obtained at different nitrobenzene conversion degrees show that degradation mainly involves successive hydroxylation steps of the aromatic ring and its subsequent opening followed by oxidation of corresponding aliphatic compounds. Our results show as primary reaction products: 4-nitrophenol, 3-nitrophenol, 2-nitrophenol, phenol and 1,3-dinitrobenzene, indicating that both hydroxylation and nitration reactions are involved. The formation of phenolic products can be explained by postulating an initial step of HO() addition to nitrobenzene ring. The mechanisms of primary reaction pathways are discussed and a detailed kinetic analysis to obtain the true primary yields of phenolic products is proposed. The relative yields observed for nitrophenol isomers do not follow the expected orientation according to deactivating characteristics of the nitro group but significantly depend on Fe(+2), Fe(+3), H(2)O(2) and O(2) concentrations. The understanding of the effect of reaction conditions on the relative product distribution benefits the application of Fenton and Fenton-like systems to waste water treatment.

Competition kinetics using the UV/H2O2 process: a structure reactivity correlation for the rate constants of hydroxyl radicals toward nitroaromatic compounds.

The rate constants for hydroxyl radical reaction toward a set of nitroaromatic substrates kS, have been measured at 25 degrees C using competition experiments in the UV/H2O2 process. For a given pair of substrates S1 and S2, the relative reactivity beta (defined as kS1/kS2) was calculated from the slope of the corresponding double logarithmic plot, i.e., of ln[S1] vs. ln[S2]. This method is more accurate and remained linear for larger conversions in comparison with the plots of ln[S1] and ln[S2] against time. The rate constants measured ranged from 0.33 to 8.6 x 10(9) M(-1)s(-1). A quantitative structure-reactivity relationship was found using the Hammett equation. Assuming sigma values to be additive, a value of -0.60 was obtained for the reaction constant rho. This value agrees with the high reactivity and the electrophilic nature of HO* radical.

Evaluation of the efficiency of photodegradation of nitroaromatics applying the UV/H2O2 technique.

Photolysis of nitroaromatic compounds in aqueous solution is a very slow and inefficient process. As already observed for a variety of organic pollutants, considerably faster degradation rates of nitrobenzene (NBE), 1-chloro-2,4-dinitrobenzene (CDNB), 2,4-dinitrophenol (DNP), and 4-nitrophenol (PNP) could be achieved, when the oxidative degradation of these compounds was initiated by hydroxyl radicals produced by UV-C photolysis of H2O2. Analysis of intermediate products formed during irradiation by HPLC and IC showed that cleavage of the aromatic ring should occur at an early stage of the oxidation process and that organic nitrogen was almost completely converted to nitrate. The optimal initial concentration of hydrogen peroxide ([H2O2]OPT) leading to the fastest oxidation rate, which depends on the initial substrate concentration ([S]0), could be evaluated using a simplified expression based on the main reactions involved in the first stages of the degradation process. Using only a minimum of kinetic and analytical information, this expression shows that the ratio R(OPT) (= [H2O2]OPT/[S]0) is related to the bimolecular rate constants for the reactions of hydroxyl radicals with substrate (kS) and H2O2 (kHP) and to the corresponding molar absorption coefficients (epsilonS, epsilonHP). Competition experiments between selected pairs of the substrates showed that their relative reactivity toward hydroxyl radicals could be correctly predicted using the same simplified approach. The results of our investigations as well as literature data support the general validity of the proposed procedure for optimizing oxidation rates of the UV/H2O2 process.

Degradation of nitroaromatic compounds by the UV-H2O2 process using polychromatic radiation sources.

The UV-H2O2 process, a standard advanced oxidation process (AOP) for water treatment, has been applied to the degradation of a series of nitroaromatic compounds (nitrobenzene, 1-chloro-2,4-dinitrobenzene, 2,4-dinitrophenol, 3-nitrophenol, 4-nitrophenol and 4-chloro-3,5-dinitrobenzoic acid) using polychromatic radiation sources. The optimal concentration of hydrogen peroxide ([H2O2]OPT) leading to the fastest degradation rate of a given substrate (S) was determined experimentally and estimated using a simplified kinetic model based on the main reactions involved in the first stages of the oxidation. We have shown that, under conditions of monochromatic irradiation, the ratio ROPT (= [H2O2]OPT/[S]0) is given by a simple mathematical expression containing only a few parameters, whereas, under conditions of polychromatic irradiation, ROPT is expressed by a complex mathematical equation (involving the spectral distribution of the lamp emission and the absorption spectra of H2O2 and the substrate). Two numerical analysis procedures are proposed for obtaining the bimolecular rate constants for the reaction of hydroxyl radicals with a substrate (kS) from this equation. The rate constants, kS, determined for the substrates investigated in this work are in agreement with the expected reactivity trend, taking into account the effects of substituents on the distribution of electron density in the aromatic ring. The methods proposed in this work offer a double advantage: i) a standard AOP may be used to evaluate the rate constants of reaction of substrates with hydroxyl radicals under polychromatic as well as under monochromatic irradiation, ii) optimal amounts of additive may be obtained using only a few parameters as predictive tools.