Indirect fibre‐optic colorimetric determination of ascorbic acid using 2‐(5‐bromo‐2‐pyridylazo)‐5‐diethylaminophenol and cloud point extraction

A new method has been developed for the indirect determination of ascorbic acid (AA) in commercial syrup preparations based on cloud point extraction (CPE) separation and preconcentration, and determination by molecular absorption spectrometry. The colorimetric method was based on the reduction of Fe(III) to Fe(II) and complexation of Fe(II) with 2‐(5‐bromo‐2‐pyridylazo)‐5‐diethylaminophenol (Br‐PADAP), followed by its extraction into Triton X‐114. Selectivity of the method was increased with the use of EDTA as a masking agent. The absorbance was measured at 742 nm. Various influencing factors on the separation and preconcentration of AA have been investigated systematically, and the optimized operation conditions were established. The proposed method allows the determination of AA in the range 5–200 µg L^?1 with a relative standard deviation of 3.0%. The detection limit was found to be 0.9 µg L^?1 for AA. This method has been applied to the determination of ascorbic acid in commercial pharmaceutical preparations. Copyright © 2011 John Wiley & Sons, Ltd.     

Comparative study of dissolved and nanoparticulate Ag effects on the life cycle of an estuarine meiobenthic copepod,Amphiascus tenuiremis

Many nanotoxicological studies have assessed the acute toxicity of nanoparticles (NPs) at high exposure concentrations. There is a gap in understanding NP chronic environmental effects at lower exposure concentrations. This study reports life-cycle chronic toxicity of sublethal exposures of polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs) relative to dissolved silver nitrate (AgNO₃) for the estuarine meiobenthic copepod, Amphiascus tenuiremis, over a range of environmentally relevant concentrations, i.e., 20, 30, 45, and 75?µg-Ag?L^?1. A concentration-dependent increase in mortality of larval nauplii and juvenile copepodites was observed. In both treatment types, significantly higher mortality was observed at 45 and 75?µg-Ag?L^?1 than in controls. In AgNO₃ exposures, fecundity declined sharply (1.8–7 fold) from 30 to 75?µg Ag?L^?1. In contrast, fecundity was not affected by PVP-AgNPs exposures. A Leslie matrix population-growth model predicted sharply 60–86% of decline in overall population sizes and individual life-stage numbers from 30–75?µg-Ag L^?1 as dissolved AgNO₃. In contrast, no population growth suppressions were predicted for any PVP-AgNPs exposures. Slower release of dissolved Ag from PVP-AgNPs and/or reduced Ag uptake in the nanoform may explain these sharp contrasts in copepod response.     

Antibacterial activity of biosynthesized gold nanoparticles using biomolecules from Lignosus rhinocerotis and chitosan

A simple, cost-effective, and environmentally friendly method is needed for synthesizing metal nanoparticles, including gold nanoparticles (AuNPs). In this study, AuNPs were synthesized with Lignosus rhinocerotis sclerotial extract (LRE) and chitosan (CS) as reducing and stabilizing agents, respectively. Different LRE concentrations from cold and hot water extraction (CWE and HWE, respectively) were used to reduce chloroauric acid (HAuCl₄) to form AuNPs. Positively charged chitosan stabilized AuNPs (CS-AuNPs) mediated by LRE exhibited a surface plasmon resonance (SPR) band at 533?nm. The CS-AuNPs synthesized using CWE had a smaller particle size (49.5?±?6.7–82.4?±?28.0?nm) compared to that of the HWE samples (80.3?±?23.4–125.3?±?41.5?nm), depending on LRE concentration. FTIR results suggested protein and polysaccharides in LRE were the sources of reducing power, reducing gold ions to AuNPs. CS-AuNPs were mostly spherical with higher LRE concentrations, whereas some triangular, pentagonal, irregular, and rod shaped AuNPs were observed at lower LRE concentrations. CS-AuNPs mediated by LRE displayed effective antibacterial activity against gram-negative (Pseudomonas aeruginosa and Escherichia coli) and gram-positive bacteria (Staphylococcus aureus and Bacillus sp.). Thus, the biosynthesized AuNPs using LRE and chitosan provide opportunities for developing stable and eco-friendly nanoparticles with effective antibacterial properties.     

177Lu‐labeled monomeric,dimeric and multimeric RGD peptides for the therapy of tumors expressing α(ν)β(3) integrins

The conjugation of peptides to gold nanoparticles (AuNPs) produces biocompatible and stable multimeric systems with target‐specific molecular recognition. Peptides based on the cyclic Arg‐Gly‐Asp (RGD) sequence have been reported as high‐affinity agents for the α(ν)β(3) integrin. The aim of this research was to prepare a multimeric system of ¹⁷⁷Lu‐labeled gold nanoparticles conjugated to c(RGDfK)C (cyclo(Arg‐Gly‐Asp‐Phe‐Lys)Cys) and to compare the radiation‐absorbed dose with that of ¹⁷⁷Lu‐labeled monomeric and dimeric RGD peptides to α(ν)β(3) integrin‐positive U87MG tumors in mice. DOTA‐GGC (1,4,7,10‐tetraazacyclododecane‐N‐N′,N″,N?‐tetraacetic acid‐Gly‐Gly‐Cys) and c(RGDfK)C peptides were synthesized and conjugated to AuNPs by a spontaneous reaction of the thiol groups. Transmission electron microscopy, ultraviolet–visible, X‐ray photoelectron spectroscopy, Raman and far‐infrared spectroscopy techniques demonstrated that AuNPs were functionalized with the peptides. For the ¹⁷⁷Lu‐AuNP‐c(RGDfK)C to be obtained, the ¹⁷⁷Lu‐DOTA‐GGC radiopeptide was first prepared and added to a solution of AuNPs followed by c(RGDfK)C (25 µl, 5 µ m ) at 18 °C for 15 min. ¹⁷⁷Lu‐DOTA‐GGC, ¹⁷⁷Lu‐DOTA‐cRGDfK and ¹⁷⁷Lu‐DOTA‐E‐c(RGDfK)₂ were prepared by adding ¹⁷⁷LuCl₃ (370 MBq) to 5 µl (1 mg/ml) of the DOTA derivative diluted with 50 µl of 1 m acetate buffer pH 5. The mixture was incubated at 90 °C in a block heater for 30 min. Radiochemical purity was determined by ultrafiltration and HPLC analyses. Biokinetic studies were accomplished in athymic mice with U87MG‐induced tumors. The radiochemical purity for all ¹⁷⁷Lu‐RGD derivatives was 96 ± 2%. ¹⁷⁷Lu‐absorbed doses per injected activity delivered to U87MG tumors were 0.357 ± 0.052 Gy/MBq (multimer), 0.252 ± 0.027 Gy/MBq (dimer) and 0.102 ± 0.018 Gy/MBq (monomer). ¹⁷⁷Lu‐labeled dimeric and multimeric RGD peptides demonstrated properties suitable for targeted radionuclide therapy of tumors expressing α(ν)β(3) integrins. Copyright © 2012 John Wiley & Sons, Ltd.     

Simultaneous determination of metformin hydrochloride and pioglitazone hydrochloride in binary mixture and in their ternary mixture with pioglitazone acid degradate using spectrophotometric and chemometric methods

In this work two well known oral hypoglycemic drugs that are administered in combination for patients with type‐II diabetes were simultaneously determined. Several spectrophotometric methods were developed and validated for the determination of metformin hydrochloride (MET), pioglitazone hydrochloride (PIO) and pioglitazone acid degradate (PIO Deg). Derivative, ratio derivative, isosbestic and chemometric‐assisted spectrophotometric methods were developed. The first derivative (D₁) method was used for the determination of MET in the range of 5–30 µg.mL^?1 and PIO in the range of 10–90 µg.mL^?1 by measuring the peak amplitude at 247 nm and 280 nm, respectively. The concentration of PIO was calculated directly at 268 nm. The first derivative of ratio spectra (DD₁) method used the peak amplitudes at 238 nm and 248.6 nm for the determination of MET in the range of 5–30 µg.mL^?1. In the isosbestic point method (ISO), the total mixture concentration was calculated by measuring the absorbance at 254.6 nm. Classical least squares (CLS), principal component regression (PCR) and partial least squares (PLS‐2) were used for the quantitative determination of MET, PIO and PIO Deg. The methods developed have the advantage of simultaneous determination of the cited components without any pre‐treatment. Resolution and quantitative determination of PIO degradate with a minimum concentration of 3 µg.mL^?1 in drug samples was done. The proposed methods were successfully used to determine each drug and the acid degradate in a laboratory‐prepared mixture and pharmaceutical preparations. The results were statistically compared using one‐way analysis of variance (ANOVA). The methods developed were satisfactorily applied to the analysis of the two drugs in pharmaceutical formulations. Copyright © 2009 John Wiley & Sons, Ltd.     

Assessment of hair and bone accumulation of beryllium by mice exposed to contaminated dusts

This study looks at the accumulation of Be in the hair and bones of mice to understand both the use of hair as a bioindicator of exposure to Be and accumulation in bones as a means to evaluate the translocation of Be. We exposed two groups of mice (C3H/HeJ) to 250 µg m^?3 of two different particles sizes of Be metal (fine and intermediate; Be‐F and Be‐I) during 3 weeks of nose‐only inhalation exposure. A control group was exposed to HEPA‐filtered air. Mice were sacrificed either 1 or 3 weeks after the end of exposure. Mice were shaved and the bones were extracted. For washed hair, the results of mice sacrificed one week after the end of exposure were 8.3 ± 1.4 µg kg^?1 hair for the control group, 114 ± 42 µg kg^?1 hair for the Be‐I group, and 159 ± 65 µg kg^?1 hair for the Be‐F group. Results for Be‐F mice sacrificed 3 weeks after the end of exposure showed an average Be concentration in washed hair of 419 ± 100 µg kg^?1, thus suggesting that excretion of Be in hair increases with time. Be concentration in bones was 6 ± 3 µg kg^?1 dry bone tissues for the control group, compared with 24 ± 7 µg kg^?1 for Be‐I and 34 ± 6 or 43 ± 8 µg kg^?1 for Be‐F in mice sacrificed 1 or 3 weeks after the end of exposure. These results demonstrate the potential of using hair and bone as bioindicators of Be exposure. Copyright © 2009 John Wiley & Sons, Ltd.     

A novel flow‐injection chemiluminescence method for determination of andrographolide in andrographis tablets

A novel method for determination of andrographolide using flow‐injection chemiluminescence (FI‐CL) analysis is described in this paper. The chemiluminescence intensity of the solution was enhanced proportionally while the concentration of andrographolide increased. Under the selected experimental conditions, the calibration curve of andrographolide was linear within the range of 0.2 to 35.0 µg mL^?1 with a linear equation of ΔI = 23.391x (µg mL^?1) + 34.191, R² = 0.9965. The detection limit (3σ) was 7.42 × 10^?2 µg mL^?1. At the case of continuous determination of andrographolide, the relative standard deviation (RSD, n = 11) was less than 1.82%. The method has been successfully applied to the determination of andrographis tablets with satisfactory results. Copyright © 2012 John Wiley & Sons, Ltd.     

Voltammetric determination of isoproterenol using multiwall carbon nanotubes-ionic liquid paste electrode

A sensitive and selective electrochemical method for the determination of isoproterenol (ISPT) was developed using multiwall carbon nanotubes and a room temperature ionic liquid (i.e. 1‐butyl‐3‐methylimidazolium hexafluoro phosphate, ([C4mim]‐[PF6])). This multiwall carbon nanotubes ionic liquid electrode (MWCNTILEE) is a very good alternative to previously described electrodes because the electrocatalytic effect is achieved without any electrode modification. The oxidation peak potentials in cyclic voltammogram of ISPT on MWCNTILEE was occurred around 470 mV vs Ag/AgCl (at pH 6.0) while this peak potential at carbon paste electrode was appeared around 605 mV at the same scan rate of 100 mV s^?1. The electrochemical parameters such as diffusion coefficient and charge transfer resistance were determined using cyclic voltammetry and electrochemical impedance spectroscopy. Under the optimized conditions, the peak current was linear to ISPT concentration over the concentration range of 1.0 to 520 µmol L^?1 using differential pulse voltammetry. The detection limit was 0.85 µmol L^?1. The proposed method was successfully applied to the determination of ISPT in both ampoules and urine samples. Copyright © 2011 John Wiley & Sons, Ltd.     

Chromatographic determination of drugs of abuse in vitreous humor using solid‐phase extraction

A simple method is presented for the simultaneous determination of morphine, 6‐acetylmorphine, codeine, cocaine, benzoylecgonine, cocaethylene, methadone and 2‐ethylidene‐1,5‐dimethyl‐3,3‐diphenylpyrrolidine (EDDP) in vitreous humor by high‐performance liquid chromatography with photodiode array detector after solid‐phase extraction with Oasis® HLB cartridges and dichloromethane as eluent. The chromatographic process was carried out using an XTerra® RP8 column (250 × 4.6 mm i.d., 5 µm particle size) and a mobile phase composed of acetonitrile and pH 6.5 phosphate buffer in gradient mode. A linear response from the detector was obtained within the concentration range of 0.1–4 µg ml^?1, with correlation coefficients higher than 0.99. The limits of detection were lower than 30 ng ml^?1 for all the drugs studied, the coefficients of variation fluctuated between 0.1 and 12.4%, and the average recoveries were higher than 78% for all the drugs except for EDDP, with a value of 66.4%. Finally, the proposed method was applied to 15 vitreous humor samples coming from individuals who had died from opiate and/or cocaine overdose, showing consumption of cocaine in 14 cases, methadone in five cases and heroin in three cases. Average concentrations of 0.30 µg ml^?1 for morphine, 0.24 µg ml^?1 for 6‐acetylmorphine, 0.10 µg ml^?1 for codeine, 0.81 µg ml^?1 for cocaine, 1.26 µg ml^?1 for benzoylecgonine, 0.15 µg ml^?1 for cocaethylene, 0.11 µg ml^?1 for methadone and 0.68 µg ml^?1 for EDDP were obtained. Copyright © 2012 John Wiley & Sons, Ltd.     

Hypothesis testing for the validation of the kinetic spectrophotometric methods for the determination of lansoprazole in bulk and drug formulations via Fe(III) and Zn(II) chelates

Point and interval hypothesis tests performed to validate two simple and economical, kinetic spectrophotometric methods for the assay of lansoprazole are described. The methods are based on the formation of chelate complex of the drug with Fe(III) and Zn(II). The reaction is followed spectrophotometrically by measuring the rate of change of absorbance of coloured chelates of the drug with Fe(III) and Zn(II) at 445 and 510 nm, respectively. The stoichiometric ratio of lansoprazole to Fe(III) and Zn(II) complexes were found to be 1:1 and 2:1, respectively. The initial‐rate and fixed‐time methods are adopted for determination of drug concentrations. The calibration graphs are linear in the range 50–200 µg ml⁻¹ (initial‐rate method), 20–180 µg ml⁻¹ (fixed‐time method) for lansoprazole‐Fe(III) complex and 120–300 (initial‐rate method), and 90–210 µg ml⁻¹ (fixed‐time method) for lansoprazole‐Zn(II) complex. The inter‐day and intra‐day precision data showed good accuracy and precision of the proposed procedure for analysis of lansoprazole. The point and interval hypothesis tests indicate that the proposed procedures are not biased. Copyright © 2010 John Wiley & Sons, Ltd.     

Comparison of acute to chronic ratios between silver and gold nanoparticles,using Ceriodaphnia dubia

As integration of nanoparticles (NPs) into products becomes more common, the need to address the paucity of chronic hazard information for aquatic environments required to determine risk potential increases. This study generated acute and chronic toxicity reference values for Ceriodaphnia dubia exposed to 20 and 100?nm silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) to generate and evaluate potential differences in acute-to-chronic ratios (ACR) using two different feeding methods. A modified feeding procedure was employed alongside the standard procedures to investigate the influence of food on organism exposure. An 8-h period before food was added allowed direct organism exposure to NP dispersions (and associated ions) without food-to-NP interactions. The AgNPs [chronic lethal median concentrations (LC50) between 18.7 and 31.9?µg/L] were substantially more toxic than AuNPs (LC50?=?21 507 to >26 384?µg/L). The modified chronic testing method resulted in greater sensitivity in AgNPs exposures. However, the modified feeding ration had less of an effect in exposures to the larger (100?nm) AgNPs compared to smaller particles (20?nm). The ACRs for AgNPs using the standard feeding ration were 1.6 and 3.5 for 20?nm and 100?nm, respectively. The ACRs for AgNPs using the modified feeding ration were 3.4 and 7.6 for 20?nm and 100?nm NPs, respectively. This supports that the addition of the standard feeding ration decreases C. dubia chronic sensitivity to AgNPs, although it must also be recognized organisms may be sensitized due to less access to food. The ACRs for 20?nm and 100?nm AuNPs (standard ration only) were 4.0 and 3.0, respectively. It is important to also consider that dissolved Ag⁺ ions are more toxic than AgNPs, based on both acute toxicity values in the cited literature and chronic toxicity thresholds generated in this study that support existing thresholds that Ag⁺ are likely protective of AgNPs effects.     

Toxicity of silver nanoparticles and ionic silver: Comparison of adverse effects and potential toxicity mechanisms in the freshwater clam Sphaerium corneum

Abstract

A range of studies has addressed possible environmental impacts of nanosilver, but most focused on acute effects in few species. Moreover, it remains unclear if toxic effects are particle-specific or mediated by released silver ions. We investigated chronic effects of nanosilver and soluble silver (AgNO₃) on the freshwater bivalve Sphaerium corneum. Animals were exposed to nanosilver (0–500?μg?Ag?L^?1) and AgNO₃ (0–318?μg?Ag?L^?1) over 28 days, and effects on reproduction and behavioral changes were assessed. To explore toxic mechanisms, we evaluated the effects on intracellular levels of reactive oxygen species (ROS) and the activity of antioxidant enzymes (superoxide dismutase, catalase, glutathione-S-transferase, glutathione peroxidase). We further explored the activity of the sodium–potassium adenosine triphosphatase (Na⁺/K⁺-ATPase). Chronic exposure to nanosilver and AgNO₃ resulted in negative effects on reproduction at concentrations of 5 and 3.18?µg?Ag?L^?1 (LOEC), respectively. ROS levels significantly increased after exposure to nanosilver at 10?µg?Ag?L^?1 and AgNO₃ at 63.5?µg?Ag?L^?1. Both forms of silver altered the activities of antioxidant enzymes. Nanosilver (500?μg?Ag?L^?1) and AgNO₃ (318?μg?Ag?L^?1) inhibited Na⁺/K⁺-ATPase activity by 82.6 and 78.9%, respectively. Nanoparticulate and soluble silver produced similar effects in S. corneum suggesting that toxicity of nanosilver is mainly mediated by dissolution of nanoparticles in the test media or after uptake by the test organisms.     

Evaluation of polyhydroxybenzophenones as α-glucosidase inhibitors

This experiment was designed to synthesize 18 kinds of polyhydroxybenzophenones by using Friedel‐Crafts reaction, and to measure the inhibitory activity on α‐glucosidase with p‐nitrophenyl‐β‐D‐galactopyranoside (PNPG) as a substrate. Here, acarbose (IC₅₀ = 1674.75 µmol L^?1) was used as the reference inhibitor. The results demonstrated that most of the target compounds had remarkable inhibitory activities on α‐glucosidase. Among all these compounds, 2,4,4′,6‐butahydroxydiphenylketone ( 11 ) was found to be the most potent α‐glucosidase inhibitor with an IC₅₀ value of 10.62 µmol L^?1. In addition, we found these compounds were competitive inhibitors through the kinetic analysis. The results suggested that such compounds might be utilized for the development of new candidates for diabetes treatment.     

Nonselective uptake of silver and gold nanoparticles by wheat

Abstract

Metallic nanoparticles (NPs) show unique reactivity to crop plants, but the uptake mechanisms remain unclear. We quantitatively evaluated the phytoavailability of particles to wheat (Triticum aestivum L.) in hydroponics upon exposure to AgNPs (15?nm) or AuNPs (13 and 33?nm). Particles were physically separated from the released Ag ions by a dialysis membrane, under which particle-specific uptake of AgNPs could be discerned. Plants did not differentiate AgNPs and AuNPs during particle uptake, with uptake rate constants of 1.1?±?0.1, 1.2?±?0.3, and 1.2?±?0.1?L?kg^?1?h^?1 for AgNPs, AuNPs (13?nm), and AuNPs (33?nm), respectively. We found little effect of particle size (13 or 33?nm AuNPs) or core composition (Ag or Au) on particle bioavailability. Plants stimulated the subsequent uptake of Evans blue stain and showed cell damage in root tips. These results imply similar physiological processes involved in particle-specific uptake of AgNPs and AuNPs. The internalization of particles was further confirmed by single particle inductively coupled plasma mass spectrometry (spICP-MS) and transmission electron microscope-energy dispersive spectrometer (TEM-EDS) analysis. The work here builds the knowledge base for the nature of particle-specific uptake of different NP types by crop plants.     

Lipid peroxidation in the kidney of rats treated with V and/or Mg in drinking water

Spontaneous and stimulated lipid peroxidation (LPO) after vanadate and magnesium treatment was studied in kidney supernatants obtained from outbred 5‐month‐old, albino male Wistar rats. The 2‐month‐old animals daily received: group I (control), deionized water to drink; group II, water solution of sodium metavanadate, NaVO₃ (SMV, 0.125 mg V ml^?1); group III, water solution of magnesium sulfate, MgSO₄ (MS, 0.06 mg Mg ml^?1); and group IV, water solution of SMV‐MS at the same concentrations as in groups II and III for V and Mg, respectively, over a 12‐week period. FeSO₄, NaVO₃ and MgSO₄ were selected as agents that may modify LPO process in in vitro conditions. Spontaneous malondialdehyde (MDA) levels in kidney supernatants increased significantly in the rats in groups II and IV, compared with groups I and III; and they were also significantly higher in all the groups of rats compared with the liver supernatants. The total antioxidant status (TAS) in groups II and IV tended to be higher too. Vanadium concentration in the kidney of the rats in groups II and IV increased, whereas the kidney Mg content in groups II, III and IV decreased, compared with levels in the liver. As the two‐way ANOVA indicated, the changes in the basal MDA level, TAS and Mg concentration in the liver of rats at combined V and Mg application only resulted from independent action of V. As far as the in vitro results are concerned, in the supernatants obtained from the rats in groups II and IV, a significant increase in MDA level was demonstrated in the presence of 30 µm of exogenous FeSO₄ as well as 30, 100, 200 and 400 µm NaVO₃ and 100, 200, 400, 600, 800 and 1000 µm MgSO₄, compared with groups I and III. The 600, 800 and 1000 µm of exogenous MgSO₄ also significantly elevated MDA production in the supernatants obtained from the rats in group III, compared with spontaneously formed MDA in the same supernatants. The three‐way ANOVA showed that the changes in LPO induced by in vitro treatment of kidney supernatants with exogenous Fe or V or Mg (600, 800 and 1000 µm ) were a consequence of independent action of those metals and they also resulted from the interactions between exogenous Fe (Fe_exog) and endogenous V (V_end) and between V_end and exogenous V (V_exog). In conclusion, V (as NaVO₃) consumed by the rats with drinking water at a dose of 12.9 mg V kg^?1 b.w. per 24 h for 12 weeks increased the basal LPO and markedly enhanced TAS in the renal tissue. Its pro‐oxidant potential was also found in in vitro conditions. The Mg dose (6 mg Mg kg^?1 b.w. per 24 h) ingested by the rats together with V (12.7 mg V kg^?1 b.w. per 24 h) neither reduced nor intensified the spontaneous LPO, compared with V‐only intoxicated animals; however, the stimulating effect of Mg on LPO was revealed in in vitro conditions.     

Stability‐indicating methods for the determination of a mixture of almitrine and raubasine by derivative spectrophotometry

A second‐derivative spectrophotometric method (²D) and a derivative ratio spectrum zero crossing (¹DD) method were used to determine raubasine and almitrine dismesylate in the presence of raubasine degradation product, using methanol as a solvent. Linear relationships were obtained in the range from 6–20 µg ml^?1 raubasine for the (²D) method and 12–24 µg ml^?1 almitrine dismesylate for the (¹DD) method. By applying these methods it was possible to determine raubasine in its pure powdered form with an accuracy of 99.93 ± 1.116 (n = 8) for the (²D) method and almitrine dismesylate with an accuracy of 99.98 ± 0.602 (n = 7) for the (¹DD) method. Laboratory‐prepared mixtures containing different ratios of raubasine, almitrine dismesylate and raubasine degradation product were analysed and the proposed methods were valid up to 50% of raubasine degradation product. They were found to be suitable stability‐indicating assay methods for raubasine and almitrine dismesylate in pharmaceutical formulations. Copyright © 2009 John Wiley & Sons, Ltd.     

Impact of Fe and Ag nanoparticles on seed germination and differences in bioavailability during exposure in aqueous suspension and soil

The potential environmental toxicity of zero‐valent iron nanoparticles (nZVI) and three types of nanosilver differing in average particle size from 1 to 20 nm was evaluated using seed germination tests with ryegrass, barley, and flax exposed to 0–5000 mg L^?1 nZVI or 0–100 mg L^?1 Ag. For nZVI, germination tests were conducted both in water and in two contrasting soils to test the impact of assumed differences in bioavailability of nanoparticles. Inhibitory effects were observed in aqueous suspensions at 250 mg L^?1 for nZVI and 10 mg L^?1 for Ag. Reduction in shoot growth was a more sensitive endpoint than germination percentage. Complete inhibition of germination was observed at 1000–2000 mg L^?1 for nZVI. For Ag, complete inhibition was not achieved. The presence of soil had a modest influence on toxicity, and inhibitory effects were observed at 300 mg nZVI L^?1 water in soil (equivalent to 1000 mg nZVI kg^?1 soil). Complete inhibition was observed at 750 and 1500 mg L^?1 in sandy soil for flax and ryegrass, respectively, while for barley 13% germination still occurred at 1500 mg L^?1. In clay soil, inhibition was less pronounced. Our results indicate that nZVI at low concentrations can be used without detrimental effects on plants and thus be suitable for combined remediation where plants are involved. Silver nanoparticles inhibited seed germination at lower concentrations, but showed no clear size‐dependant effects, and never completely impeded germination. Thus, seed germination tests seem less suited for estimation of environmental impact of Ag. © 2010 Wiley Periodicals, Inc. Environ Toxicol 2012.     

Targeted 64Cu‐labeled gold nanoparticles for dual imaging with positron emission tomography and optical imaging

Gold nanoparticles (AuNPs) have been used for many years in cancer treatment mainly for brachytherapy, but in the last 15 years, the focus has shifted to the development of ultrasmall target‐specific AuNPs with homogeneous size and, ultimately, tailored shapes for use in various imaging modalities such as computed tomography (CT), Raman, or photoacoustic imaging. Here, we report on the development of tumor‐specific AuNPs as diagnostic tools intended for the dual detection of prostate cancer via optical imaging (OI) and positron emission tomography (PET). The AuNPs were decorated with a near‐infrared dye and NODAGA chelator for complexation with radiometals. Radiolabeling with ⁶⁴Cu was performed either indirect by complexation with NODAGA‐AuNPs or by direct reduction of [⁶⁴Cu]Cu(0) onto the surface of the AuNPs. Both methods yielded stable ⁶⁴Cu‐AuNPs with radiochemical yield more than 95% confirmed by HPLC. ⁶⁴Cu‐AuNPs were evaluated in a dual‐imaging setting in vitro and in vivo and exhibited favorable diagnostic properties concerning detection, biodistribution, and clearance. Furthermore, the first therapeutic properties of the ⁶⁴Cu‐AuNPs were evaluated in vitro concerning acute and long‐term toxicity, indicating that these ⁶⁴Cu‐AuNPs could be used in therapeutic concepts in the future.     

High dose methotrexate population pharmacokinetics and Bayesian estimation in patients with lymphoid malignancy

The purpose of present study was to develop a population pharmacokinetic model of high dose methotrexate (HD‐MTX) infusion in patients with lymphoid malignancy, to investigate the biological and clinical covariates related to the drug distribution and elimination. It is also the purpose to propose a limited sampling strategy (LSS) for the estimation of the time above the threshold (0.2 µmol·L^?1). A total 82 patients with lymphoid malignancy were involved in the study. A pharmacokinetic model was developed using nonlinear mixed‐effect model. The influence of demographic characteristics, biological factors, and concurrent administration were investigated. The final predictive performance was validated by bootstrap and cross‐validation. Bayesian estimation was evaluated. The pharmacokinetics of HD‐MTX was described by a two‐compartment model. The pharmacokinetic parameters and the inter‐individual variability were as follows: the clearance CL, 7.45 L·h^?1 (inter‐individual variability 50.6%), the volume of the central and peripheral compartment V₁, 25.9 L (22.5%), V₂, 9.23 L (97.8%), respectively, and the intercompartmental clearance Q, 0.333 L·h^?1 (70.4%). The influence of serum creatinine on CL and weight on V₁ was retained in the final model. The protocol involved one sampling time at 44 h after the start of the infusion, allowing one to predict the time at which the MTX concentration reached the expected threshold (0.2 µmol·L^?1). Serum creatinine and weight showed significant influence on methotrexate CL and V₁, respectively. Furthermore, a Bayesian estimation based on the covariates and 44 h sample was developed, allowing prediction of the individual methotrexate pharmacokinetic parameters and the time to 0.2 µmol·L^?1. Copyright © 2009 John Wiley & Sons, Ltd.