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In the present study, β-cyclodextrin modified magnetic graphene oxide/cellulose (CN/IGO/Cel) was fabricated for removal of Cd(II) ions. The material was characterized through various analytical techniques like FTIR, XRD, TGA/DTA, SEM, TEM, and XPS. The point of zero charge of the material was obtained as 5.38. The controllable factors were optimized by Taguchi design and optimum values were: adsorbent dose-16 mg, equilibrium time-40 min, and initial concentration of Cd(II) ions-40 mg/L. The material shows high adsorption capacity (303.98 mg/g). The good fitting of Langmuir model to adsorption data (R 2  = 0.9918-0.9936) revealed the monolayer coverage on adsorbent surface. Statistical physics model M 2 showed best fitting to adsorption data (R 2  > 0.997), suggesting the binding of Cd(II) ions occurred on two different receptor sites (n). Stereographically n > 1 confirming vertical multi-molecular mechanisms of Cd(II) ions adsorption on CN/IGO/Cel surface. The adsorption energies (E 1  = 23.71-28.95 kJ/mol; E 2  = 22.69-29.38 kJ/mol) concluded the involvement of physical forces for Cd(II) ions adsorption. Kinetic data fitted well to fractal-like pseudo first-order model (R 2  > 0.9952), concluding the adsorption of Cd(II) ions occurred on energetically heterogeneous surface. The kinetic analysis shows that both the film-diffusion and pore-diffusion were responsible for Cd(II) ions uptake. XPS analysis was utilized to explain the adsorption mechanism of Cd(II) ions onto CN/IGO/Cel., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Beta-cyclodextrin (β-CD) is a cyclic oligosaccharide consisting of seven glucose units. β-CD is increasingly used in food research to reduce cholesterol due to its affinity for non-polar molecules such as cholesterol and as a natural additive. The purpose of this study was to evaluate the effect of curd washing in ewe's milk cheese on the reduction in cholesterol by β-CD from pasteurized ewe's milk Manchego cheese and the characteristics of its main components: milk, lipids, and flavor. An approximately 98.45% cholesterol reduction was observed in washed experimental cheeses that were treated by using β-CD. The remaining residual β-CD from the effect of curd washing was 0.15% in mature cheese, of the initial 1% β-CD treatment of the milk. The chemical properties (fat, moisture, and protein) did not change as a result of the curd washing with or without β-CD. The curd washing with or without β-CD on the levels of the various lipid fraction (fatty acids, triglycerides, and phospholipids) were comparable in treated and untreated cheeses. The effects of curd washing and the β-CD treatment did not significantly affect flavor components or short chain free fatty acids. The β-CD molecules were edible and nontoxic; as a result, they could be used safely in cholesterol removal processing in cheese manufacturing, improving the reduction in residual β-CD by curd washing by 85%. Therefore, the present study suggests that curd washing combined with β-CD is an effective process for cholesterol removal in Manchego cheese, preserving its desirable properties.

Background: At present, the research on achiral drug and pesticide residue detection methods is still the mainstay at home and abroad, and there is still a lack of systematic research on the enantiomeric analysis of chiral drugs and pesticides., Objective: In order to prepare a novel chiral stationary phase, whose "multi-mode" chiral separation chromatographic performance and its utility was verified., Method: An S-(-)-2-benzylamino-1-phenylethanol mono-derivative β-cyclodextrin bonded stationary phase (BzCSP) was prepared based on the "thiol-ene" addition reaction. The chiral compounds including four types of chiral compounds were used as "probes," and their chiral chromatographic properties were evaluated. Furthermore, a new LC-MS/MS method for the determination of the enantiomeric residues of three chiral pesticides in five kinds of fruits and vegetables was established., Results: The study found that the novel stationary phase was suitable for a variety of chromatographic modes (normal phase mode, reversed-phase mode, polar organic mode). The resolutions of hexaconazole (Hex), tebuconazole (Teb), and triticonazole (Trit) enantiomers could be up to 2.31, 1.68, and 1.48, respectively, within 30 min under reversed-phase chromatography. Based on the optimal chromatographic and mass spectrum conditions, a new LC-MS/MS quantitative method for the Hex, Teb, and Trit enantiomers was established by multi-reaction positive ion monitoring (MRM). The detection limits (LODs) of enantiomers were less than 0.89 µg/kg for Hex, 0.93 µg/kg for Teb, and 0.93 µg/kg for Trit, and the averaged recoveries of enantiomers were in the range of 75.8-106.3% for Hex, 77.4-116.3% for Teb, and 78.7-113.4% for Trit. The method had good reproducibility with the RSDs (<5%) for intraday and (<7%) for interday., Conclusions: The established method had the characteristics of good selectivity, high sensitivity, strong resistance to matrix interference, and good reproducibility. It is indicated that the stationary phase prepared by the "thiol-ene" addition reaction is a new type of multi-mode stationary phase, which has a good development value., Highlights: The study reported a new method for the rapid preparation of a rare "multi-mode" chiral stationary phase BzCSP based on the "thiol-ene" addition reaction and verified the practicability of BzCSP including good selectivity, high sensitivity, strong resistance to matrix interference, and good reproducibility., (© The Author(s) 2022. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: To determine if commercially available mouthwash with β-cyclodextrin and citrox (bioflavonoids) (CDCM) could decrease the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) salivary viral load., Methods: In this randomized controlled trial, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR-positive patients aged 18-85 years with asymptomatic to mild coronavirus disease 2019 (COVID-19) symptoms for <8 days were recruited. A total of 176 eligible patients were randomly assigned (1:1) to CDCM or placebo. Three rinses daily were performed for 7 days. Saliva sampling was performed on day 1 at 09.00 (T1), 13.00 (T2) and 18.00 (T3). On the following 6 days, one sample was taken at 15.00. Quantitative RT-PCR was used to detect SARS-CoV-2., Results: The intention-to-treat analysis demonstrated that, over the course of 1 day, CDCM was significantly more effective than placebo 4 hours after the first dose (p 0.036), with a median percentage (log 10 copies/mL) decrease T1-T2 of -12.58% (IQR -29.55% to -0.16%). The second dose maintained the low median value for the CDCM (3.08 log 10 copies/mL; IQR 0-4.19), compared with placebo (3.31 log 10  copies/mL; IQR 1.18-4.75). At day 7, there was still a greater median percentage (log 10 copies/mL) decrease in salivary viral load over time in the CDCM group (-58.62%; IQR -100% to -34.36%) compared with the placebo group (-50.62%; IQR -100% to -27.66%). These results were confirmed by the per-protocol analysis., Conclusions: This trial supports the relevance of using CDCM on day 1 (4 hours after the initial dose) to reduce the SARS-CoV-2 viral load in saliva. For long-term effect (7 days), CDMC appears to provide a modest benefit compared with placebo in reducing viral load in saliva., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

An open tubular capillary electrochromatography column was prepared by immobilizing β-cyclodextrin on the inner wall of pretreated capillary via noncovalent adsorption of polydopamine. The resulting coating layer on the capillary was characterized by scanning electron microscopy and Fourier transform infrared spectroscopy. Electroosmotic flow was studied to evaluate the variation of the immobilized columns. The prepared columns showed good chiral separation performance toward five proton pump inhibitors including lansoprazole, pantoprazole, tenatoprazole, rabeprazole, and omeprazole. The influences of β-cyclodextrin concentration, coating time, buffer pH, buffer concentration, and applied voltage on separation were investigated. In the optimum conditions, the enantiomers of five analytes were fully resolved within 15 min with high resolutions of 4.57 to 8.13. The method was extensively validated in terms of accuracy, precision, and linearity and proved to be robust. The relative standard deviation values for migration times and peak areas of the analytes representing intraday and interday were less than 1.9 and 3.6%, respectively. Further, the polydopamine/β-cyclodextrin coated capillary column could be successively used over 100 runs without showing significant decrease in the separation efficiency., (© 2021 Wiley-VCH GmbH.)

1-Pyrrolines are important intermediates of active natural products, such as the 2,5-dialkyl-1-pyrroline derivatives found in fire ant venoms. Here, 5-hexyl-2-methyl-3,4-dihydro-2 H -pyrrole was synthesized by the enzymatic transamination/cyclization of 2,5-undecadione, and enantiodifferenciation was successfully achieved by capillary electrophoresis with sulfobutyl ether-β-cyclodextrin as the chiral selector. The rationale of the enantiomeric discrimination was based on the results of a docking simulation that revealed the higher affinity of ( S )-5-hexyl-2-methyl-3,4-dihydro-2 H -pyrrole for the sulfobutyl ether-β-cyclodextrin.

α-Mangostin (MGS) exhibits various pharmacological activities, including antioxidant, anticancer, antibacterial, and anti-inflammatory properties. However, its low water solubility is the major obstacle for its use in pharmaceutical applications. To increase the water solubility of MGS, complex formation with beta-cyclodextrins (βCDs), particularly with the native βCD and/or its derivative 2,6-dimethyl-β-CD (DMβCD) is a promising technique. Although there have been several reports on the adsorption of βCDs on the lipid bilayer, the release of the MGS/βCDs inclusion complex through the biological membrane remains unclear. In this present study, the release the MGS from the two different βCDs (βCD and DMβCD) across the lipid bilayer was investigated. Firstly, the adsorption of the free MGS, free βCDs, and inclusion complex formation was studied by conventional molecular dynamics simulation. The MGS in complex with those two βCDs was able to spontaneously release free MGS into the inner membrane. However, both MGS and DMβCD molecules potentially permeated into the deeper region of the interior membrane, whereas βCD only adsorbed at the outer membrane surface. The interaction between secondary rim of βCD and the 1-palmitoeyl-2-oleoyl-glycero-3-phosphocholine (POPC) phosphate groups showed the highest number of hydrogen bonds (up to 14) corresponding to the favorable location of βCD on the POPC membrane. Additionally, the findings suggested that electrostatic energy was the main driving force for βCD adsorption on the POPC membrane, while van der Waals interactions played a predominant role in DMβCD adsorption. The release profile of MGS from the βCDs pocket across the lipid bilayer exhibited two energy minima along the reaction coordinate associated with the permeation of the MGS molecule into the deeper region of the POPC membrane.

Clozapine (CLZ) is an atypical antipsychotic medication used in the treatment of schizophrenia and is poorly soluble in water (0.05 mM). In this study, we have investigated the effect of β-cyclodextrin (CD) and its derivatives on the solubility of CLZ. The solubility of the CLZ was measured to generate a phase solubility diagram, and the interaction between CLZ and sulfobutyl ether-β-cyclodextrin (SBE-β-CD) in aqueous solution was observed by 1 H- and 2D rotating-frame Overhauser enhancement spectroscopy (ROESY)-NMR methods. Moreover, the synergistic effect of SBE-β-CD and water-soluble polymers, including polyvinylpyrrolidone, hydroxypropyl methylcellulose, carboxymethylcellulose sodium salt, polyvinyl alcohol, sodium alginate, and propylene glycol alginate (PGA), on the solubility of CLZ was investigated. The results show that the solubility of CLZ with 1 w/v% PGA was 7.6 mM, which was almost four times greater than that of CLZ without PGA in a 15 mM SBE-β-CD solution. In contrast, the solubility of CLZ with 1 w/v % PGA in an aqueous solution decreased by one-third relative to that of CLZ in a 15 mM SBE-β-CD solution. 2D ROESY-NMR indicated that a CLZ/SBE-β-CD/PGA ternary complex formed. It was found that the combination of PGA and SBE-β-CD enhanced the solubility of CLZ.

In this article, we describe the quantitative characterization of a gold nanoneedle ion channel probe and demonstrate the utility of this probe for spatially resolved detection of a small molecule using ion channel activity. Our report builds on recent reports of Ide and co-workers, who reported the use of an etched gold wire modified with a poly(ethylene) glycol monolayer as a support for a lipid bilayer and subsequent single ion channel recordings. Although this nanoneedle electrode approach was reported previously, in our report, we investigate the effects of several operational parameters on the performance of the ion channel measurement and electrochemical phenomenon that occur in the nanoconfined space between the supported bilayer and the gold electrode. More specifically, we address the effects of length of the supporting monolayer and the composition of the electrolyte baths on channel current measurements and provide a quantitative description of what carries current at the working electrode (double-layer charging). In addition, we demonstrate the ability to control the direction of protein insertion (tip side vs bath side) with freely diffusing protein, which has not been previously reported, with the former method (tip side) enabling single-molecule detection of β-cyclodextrin (βCD) using a reconstituted α-hemolysin channel. Finally, anticipating future use of a nanoneedle-based biological nanopore probe in a scanned-probe microscopy, we demonstrate the ability to quantify and spatially resolve the concentration of βCD molecules in a microfluidic channel. We believe, in the long term, the described nanoneedle-based biological nanopore probe can be employed in, for example, scanning ion conductance microscopy using ion channels.

The present study evaluated influence of boiled sausages consumption fortified with β-CD-I 2 on the urinary iodine excretion (UIE) level of volunteers. Median urinary UIE level was increased from 58.02 (24.0-175.4) μg/L to 110.6 (20.5-231.6) μg/L during 10 days. Thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels were determined by radio immunoassay analysis. As it was expected, intake of sausages fortified with β-CD-I 2 resulted in rise of FT4 level from 1.1 (0.95-1.25) to 1.23 (1.07-1.63) ng/dL, whereas TSH level decreased from 1.53 (0.47-3.37) mIU/L to 1.1 (0.51-3.17) mIU/L. A dynamic gastrointestinal model in vitro was used in order to determine possibility of 3,5-diiodotyrosine (DIT) formation during consumption of the fortified sausages. The DIT concentration was determined by HPLC-MS method and was found to be 0.38 ng/mL in sausage dialyzate. These findings indicate that β-CD-I 2 introduction as an iodine carrier in boiled sausages may help to improve iodine status and to control organic iodine species concentration., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Purpose: The objective of this study was to compare the stability of recently approved Captisol-stabilized propylene glycol-free melphalan injection (Evomela™) against currently marketed propylene glycol-based melphalan injection. The products were compared as reconstituted solutions in vials as well as admixture solutions prepared from normal saline in infusion bags., Methods: Evomela and propylene glycol-based melphalan injection were reconstituted in normal saline and organic custom diluent, respectively, according to their package insert instructions. The reconstituted solutions were diluted in normal saline to obtain drug admixture solutions at specific drug concentrations. Stability of the solutions was studied at room temperature by assay of melphalan and determination of melphalan-related impurities., Results: Results show that based on the increase in total impurities in propylene glycol-based melphalan injection at 0.45 mg/mL, Evomela admixture solutions are about 5, 9, 15 and 29 times more stable at concentrations of 0.45, 1.0, 2.0 and 5.0 mg/mL, respectively. Results confirmed that reconstituted Evomela solution can be stored in the vial for up to 1 h at RT or for up to 24 h at refrigerated temperature (2-8 °C) with no significant degradation. After storage in the vial, it remains stable for an additional 3-29 h after preparation of admixture solution in infusion bags at concentrations of 0.25-5.0 mg/mL, respectively. In addition, Evomela solution in saline, at concentration of 5.0 mg/mL melphalan was bacteriostatic through 72 h storage at 2-8 °C., Conclusion: Formulation of melphalan with Captisol technology significantly improved stability compared to melphalan hydrochloride reconstituted with propylene-glycol based diluents.

Consumers demand more alternatives of riskless antibacterial agents to prevent microbial contamination in food industry. Oxidized carbohydrate may be a potential option as new antibacterial agent. However, the relatively weak antibacterial property of oxidized carbohydrate is not satisfactory. In this paper, dialdehyde β-cyclodextrins with different oxidation degree were prepared by periodate oxidation and their antibacterial properties were systematically studied. The results showed that multi-aldehyde groups were successfully introduced into β-cyclodextrin molecules by periodate oxidation. The aqueous solubility and stability of dialdehyde β-cyclodextrins were improved as expected. It is interesting that dialdehyde β-cyclodextrins possessed outstanding antibacterial activity against both Gram-positive and Gram-negative bacteria. The minimal inhibitory concentrations against E. coli, S. aureus and B. subtilis reached 0.63, 1.25 and 0.63 mg/mL, respectively. Moreover, dialdehyde β-cyclodextrins effectively inhibited bacterial growth on the surface of apples. The results demonstrated that oxidized oligosaccharide with multi-aldehyde groups and good dispersibility in aqueous solution possessed satisfactory antibacterial activity, which can be used as new antibacterial agent in food industry., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Lipid rafts are major structural components in plasma membranes that play critical roles in many biological processes including virus infection. However, few reports have described the relationship between lipid rafts and porcine rotavirus (PRV) infection. In this study, we investigated whether or not the locally high concentrations (3-5 fold) of cholesterol present in lipid rafts are required for PRV infection, and further examined which stages of the infection process are most affected., Results: When cellular cholesterol was depleted by methyl-β-cyclodextrin (MβCD), PRV infectivity significantly declined in a dose-dependent manner. This inhibition was partially reversed upon reintroduction of cholesterol into the system. This was corroborated by the co-localization of PRV with a recombinant, GPI-anchored green fluorescent protein, which functioned as a marker for membranous regions high in cholesterol and indicative of lipid rafts. Changes in virus titer and western blot analyses indicated that depletion of cellular cholesterol with MβCD had no apparent effect on PRV adsorption; however, depletion of cholesterol significantly restricted entry and post-entry of PRV into the cell. Both points of inhibition were restored to near normal levels by the addition of exogenous cholesterol., Conclusions: We conclude from these studies that membrane-based cholesterol and in particular that localized to lipid rafts, is an indispensable biomolecule for PRV infection, and that cholesterol-based control of the infection process takes place during entry and immediately post-entry into the cell.

Molecularly imprinted polymers were prepared using the molecular structure analogs of sanshool as template molecule, 2-vinylpyridine and β-cyclodextrin as double functional monomers, ethylene dimethacrylate as cross linker, and azobisisobutyronitrile as initiator. The structural characteristics of the polymers were determined by Fourier-transform infrared spectroscopy and scanning electron microscopy. Dynamic adsorption and isothermal adsorption were also investigated. The molecularly imprinted polymers were used to prepare a molecularly imprinted solid-phase extraction column in order to separate acid amide components from pepper oil resin derived from Chinese prickly ash (Zanthoxylum bungeanum). After eluting, the percentage of acid amide components was enhanced to 92.40 ± 1.41% compared with 23.34 ± 1.21% in the initial pepper oil resin, indicating good properties of purification of molecularly imprinted polymers and potential industrial application., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Water-insoluble β-cyclodextrin polymer was synthesized by chemical cross-linking using epichlorohydrin (EPI) as a cross-linker agent. The produced water-insoluble polymer was used as a sorbent for the micro-solid phase extraction (μ-SPE) of benzene, toluene, ethylbenzene and xylenes (BTEX) from water samples. The μ-SPE device consisted of a sealed tea bag envelope containing 15mg of sorbent. For the evaluation of the extraction efficiency, parameters such as extraction and desorption time, desorption solvent and salt concentration were investigated. At an extraction time of 30min in the course of the extraction process, analytes were extracted from a 10mL aqueous sample solution. The analytes were desorbed by ultrasonication in 200μL of acetonitrile for 20min. Analysis of the analytes was done by a gas chromatography-flame ionization detector (GC-FID) system. The enrichment factor (EF) was found to be in the range 23.0-45.4 (EF max =50.0). The method provided linearity ranges of between 0.5 and 500.0ng/mL (depending on the analytes), with good coefficients of determination (r 2 ) ranging between 0.997 and 0.999 under optimized conditions. Detection limits for BTEX were in the range of between 0.15 and 0.60ng/mL, while corresponding recoveries were in the range of 46.0-90.0%. The relative standard deviation of the method for the analytes at 100.0ng/mL concentration level ranged from 5.5 to 11.2% (n=5). The proposed method was concluded to be a cost effective and environmentally-friendly extraction technique with ease of operation and minimal usage of organic solvent., (Copyright © 2017 Elsevier B.V. All rights reserved.)

This contribution reports the synthesis, characterization and capillary electrophoretic application of heptakis-(6-O-sulfobutyl-ether)-β-cyclodextrin sodium salt, (6-(SB) 7 -β-CD). The compound was obtained through a five-steps synthesis and it represents the first example of single-isomer sulfobutylated cyclodextrin that carries the negatively charged functions exclusively on its primary side and it is unmodified on the lower rim. The purity of each intermediate was determined by appropriate liquid chromatographic methods, while the isomeric purity of the final product was established by an ad-hoc developed HPLC method based on a CD-Screen-IEC column. The structural identification of 6-(SB) 7 -β-CD was carried out by 1D, 2D NMR spectroscopy and ESI-MS. The chiral separation ability of 6-(SB) 7 -β-CD was studied by chiral capillary electrophoresis using the single-isomer host as a background electrolyte additive to separate the enantiomers of a representative set of pharmacologically significant model compounds such as verapamil, dapoxetine, ondansetron, propranolol, atenolol, metoprolol, carvedilol, terbutaline, amlodipine and tadalafil. The enantiomer migration order and the effects of the selector concentration on the enantiorecognition properties were investigated. NMR spectroscopy was applied to deepen and further confirm the host-guest interactions and in the case of the model compound dapoxetine a potential representation for the supramolecular assembly was developed based on the dataset collected by the extensive 2D NMR analysis. This single-isomer chiral selector offers a new alternative to the widely applied randomly sulfobutylated- and sulfated-beta-cylodextrins as well as to the single-isomer sulfated and carboxymethylated derivatives in chiral separations., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The cost-effective and energy-efficient removal of organic micropollutants (MPs) from water and wastewater is challenging. The objective of this research was to evaluate the performance of porous β-cyclodextrin polymers (P-CDP) as adsorbents of MPs in aquatic matrixes. Adsorption kinetics and MP removal were measured in batch and flow-through experiments for a mixture of 83 MPs at environmentally relevant concentrations (1 μg L -1 ) and across gradients of pH, ionic strength, and natural organic matter (NOM) concentrations. Performance was benchmarked against a coconut-shell activated carbon (CCAC). Data reveal pseudo-second-order rate constants for most MPs ranging between 1.5 and 40 g mg -1 min -1 for CCAC and 30 and 40000 g mg -1 min -1 for P-CDP. The extent of MP removal demonstrates slower but more uniform uptake on CCAC and faster but more selective uptake on P-CDP. Increasing ionic strength and the presence of NOM had a negative effect on the adsorption of MPs to CCAC but had almost no effect on adsorption of MPs to P-CDP. P-CDP performed particularly well for positively charged MPs and neutral or negatively charged MPs with McGowan volumes greater than 1.7 (cm 3 mol -1 )/100. These data highlight advantages of P-CDP adsorbents relevant to MP removal during water and wastewater treatment.

Capillary electrophoresis frontal analysis (CE-FA) can be used to determine binding affinity of molecular interactions. However, its current data processing method mandate specific requirement on the mobilities of the binding pair in order to obtain accurate binding constants. This work shows that significant errors are resulted when the mobilities of the interacting species do not meet these requirements. Therefore, the applicability of CE-FA in many real word applications becomes questionable. An electrophoretic mobility-based correction method is developed in this work based on the flux of each species. A simulation program and a pair of model compounds are used to verify the new equations and evaluate the effectiveness of this method. Ibuprofen and hydroxypropyl-β-cyclodextrinare used to demonstrate the differences in the obtained binding constant by CE-FA when different calculation methods are used, and the results are compared with those obtained by affinity capillary electrophoresis (ACE). The results suggest that CE-FA, with the mobility-based correction method, can be a generally applicable method for a much wider range of applications., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Methyl-β-cyclodextrin (MβCD) reduces lysosomal cholesterol accumulation in Niemann-Pick disease type C1 (NPC1) patient fibroblasts. However, the pharmacological activity of MβCD reported by different laboratories varies. To determine the potential causes of this variation, we analyzed the mass spectrum characteristics, pharmacological activity of three preparations of MβCDs, and the protein expression profiles of NPC1 patient fibroblasts after treatment with different sources of MβCDs. Our data revealed varied mass spectrum profiles and pharmacological activities on the reduction of lysosomal cholesterol accumulation in NPC1 fibroblasts for these three preparations of MβCDs obtained from different batches and different sources. Furthermore, a proteomic analysis showed the differences of these three MβCD preparations on amelioration of dysregulated protein expression levels in NPC1 cells. The results demonstrate the importance of prescreening of different cyclodextrin preparations before use as a therapeutic agent. A combination of mass spectrum analysis, measurement of pharmacological activity, and proteomic profiling provides an effective analytical procedure for characterization of cyclodextrins for therapeutic applications.

The negative health impact of polycyclic aromatic hydrocarbons (PAHs) and differences in pharmacological activity of enantiomers of chiral molecules in humans highlights the need for analysis of PAHs and their chiral analogue molecules in humans. Herein, the first use of cyclodextrin guest-host inclusion complexation, fluorescence spectrophotometry, and chemometric approach to PAH (anthracene) and chiral-PAH analogue derivatives (1-(9-anthryl)-2,2,2-triflouroethanol (TFE)) analyses are reported. The binding constants (K b ), stoichiometry (n), and thermodynamic properties (Gibbs free energy (ΔG), enthalpy (ΔH), and entropy (ΔS)) of anthracene and enantiomers of TFE-methyl-β-cyclodextrin (Me-β-CD) guest-host complexes were also determined. Chemometric partial-least-square (PLS) regression analysis of emission spectra data of Me-β-CD-guest-host inclusion complexes was used for the determination of anthracene and TFE enantiomer concentrations in Me-β-CD-guest-host inclusion complex samples. The values of calculated K b and negative ΔG suggest the thermodynamic favorability of anthracene-Me-β-CD and enantiomeric of TFE-Me-β-CD inclusion complexation reactions. However, anthracene-Me-β-CD and enantiomer TFE-Me-β-CD inclusion complexations showed notable differences in the binding affinity behaviors and thermodynamic properties. The PLS regression analysis resulted in square-correlation-coefficients of 0.997530 or better and a low LOD of 3.81×10 -7 M for anthracene and 3.48×10 -8 M for TFE enantiomers at physiological conditions. Most importantly, PLS regression accurately determined the anthracene and TFE enantiomer concentrations with an average low error of 2.31% for anthracene, 4.44% for R-TFE and 3.60% for S-TFE. The results of the study are highly significant because of its high sensitivity and accuracy for analysis of PAH and chiral PAH analogue derivatives without the need of an expensive chiral column, enantiomeric resolution, or use of a polarized light., (Published by Elsevier B.V.)

The aim of this study was to synthesize and characterize the octenyl succinic-β-cyclodextrin (OS-β-CD) and assess its application as a potential emulsion stabilizer. OS-β-CD was prepared by esterifying β-CD with OSA under alkaline conditions. The properties of OS-β-CD were characterized by Fourier transform infrared, 13 C and 1 H NMR spectroscopy, X-ray diffraction (XRD), which demonstrated that OS groups had been introduced into the β-CD molecules and most of OS substitution occurred at the C-6 hydroxyl group of glycosyl units. The properties of emulsions stabilized by β-CD and OS-β-CD were evaluated via surface and interface tensiometry, determination of the creaming index and droplet size. The results showed that emulsions stabilized by β-CD broke just after 24h storage at 25°C. The emulsions prepared by OS-β-CD with all degree of substitution (DS) possessed a smaller oil droplet size and improved storage stability compared with that of the emulsion generated using β-CD., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Recalcitrant organic groundwater contaminants, such as 1,4-dioxane, may require strong oxidants for complete mineralization. However, their efficacy for in-situ chemical oxidation (ISCO) is limited by oxidant decay and reactivity. Hydroxypropyl-β-cyclodextrin (HPβCD) was examined for its ability to stabilize aqueous-phase ozone (O 3 ) and prolong oxidation potential through inclusion complex formation. Partial transformation of HPβCD by O 3 was observed. However, HPβCD proved to be sufficiently recalcitrant, because it was only partially degraded in the presence of O 3 . The formation of a HPβCD:O 3 clathrate complex was observed, which stabilized decay of O 3 . The presence of HPβCD increased the O 3 half-life linearly with increasing HPβCD:O 3 molar ratio. The O 3 half-life in solutions increased by as much as 40-fold relative to HPβCD-free O 3 solutions. Observed O 3 release from HPβCD and indigo oxidation confirmed that the formation of the inclusion complex is reversible. This proof-of-concept study demonstrates that HPβCD can complex O 3 while preserving its reactivity. These results suggest that the use of clathrate stabilizers, such as HPβCD, can support the development of a facilitated-transport enabled ISCO for the O 3 treatment of groundwater contaminated with recalcitrant compounds., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The aim of this study was to evaluate hot-melt extrusion (HME) as a continuous process to form cyclodextrin (CD) inclusion complexes in order to increase the solubility and dissolution rate of itraconazole (ITZ), a class II model drug molecule of the Biopharmaceutics Classification System. Different CD derivatives were tested in a 1:1 (CD:ITZ) molar ratio to obtain CD ternary inclusion complexes in the presence of a polymer, namely Soluplus ® (SOL). The CD used in this series of experiments were β-cyclodextrin (βCD), hydroxypropyl-β-cyclodextrin (HPβCD) with degrees of substitution of 0.63 and 0.87, randomly methylated β-cyclodextrin (Rameb ® ), sulfobutylether-β-cyclodextrin (Captisol ® ) and methyl-β-cyclodextrin (Crysmeb ® ). Rheology testing and mini extrusion using a conical twin screw mini extruder were performed to test the processability of the different CD mixtures since CD are not thermoplastic. This allowed Captisol ® and Crysmeb ® to be discarded from the study due to their high impact on the viscosity of the SOL/ITZ mixture. The remaining CD were processed by HME in an 18mm twin screw extruder. Saturation concentration measurements confirmed the enhancement of solubility of ITZ for the four CD formulations. Biphasic dissolution tests indicated that all four formulations had faster release profiles compared to the SOL/ITZ solid dispersion. Formulations of HPβCD 0.63 and Rameb ® even reached 95% of ITZ released in both phases after 1h. The formulations were characterized using thermal differential scanning calorimetry and attenuated total reflectance infra-red analysis. These analyses confirmed that the increased release profile was due to the formation of ternary inclusion complexes., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Anthocyanin-rich powders and aqueous extracts, with high antioxidant activities, were obtained from black bean seed coats and applied to colour a sport beverage. Idaho and Otomi bean coats were extracted in water-citric acid 2% (1/50, w/v), stirring for 4h at 40°C. Anthocyanins from Idaho and Otomi extracts (1.83mg and 1.02mg C3G/g, respectively) were applied to a commercially available sport beverage, with and without 2% β-cyclodextrin (βCD) under light and darkness conditions for 10days, and stored at 4°C and 25°C for 6weeks. At different light and storage conditions, anthocyanin degradation fitted a first-order reaction model. All bean coat anthocyanins combined with βCD showed extended half-life (up to 13months), higher D-values (up to 43months) and fewer differences in colourimetric properties (lightness, chroma and hue angle) under darkness and 4°C conditions. These black bean coat aqueous extracts and powders might represent natural alternatives to synthetic colorants, ecologically extracted, and with a high antioxidant potential., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

A novel dispersive micro-SPE method with trace poly-β-CD wrapped multiwalled carbon nanotubes as sorbents was applied to extract flavonoids in honey samples. The analytes were then determined by CE with LED-induced fluorescence detection. The influencing parameters, such as the sorbent concentration, extraction time, and eluent type, were properly optimized. The established method had the advantages of simplicity, low consumption of sorbent amount (0.009 mg) and organic solvent (100 μL), and high sensitivity, meeting the principle of green chemistry. Under the optimum conditions, the sorbents allowed the extraction and preconcentration of the flavonoids with enrichment factors in the range from 78 to 166. The recovery study performed at two different fortification levels provided an average recovery >91%. LODs for all the compounds ranged from 0.07 to 17.99 ng/mL. These results demonstrated that the proposed method could be used as a convenient and efficient extraction technique for analysis of flavonoids in different honey matrices., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Omega-3 nutraceuticals are extensively used as health supplements worldwide. Various administration forms for delivery of omega-3 are available. However, the niche omega-3 tablets have so far remained unexplored. In this work tablets containing 25-40% (w/w) omega-3 oil as triglycerides or ethyl esters were prepared utilizing a direct compaction grade powder with β-cyclodextrin as encapsulating agent. It was found that powders with up to 35% (w/w) triglyceride oil and 30% (w/w) ethyl ester oil, respectively, can be directly compressed into tablets of excellent quality. Physical properties of omega-3 containing powders and tablets are described. The powder X-ray diffractograms of the powders and crushed tablets show evidence of the formation of new crystalline phases not present in β-cyclodextrin. In addition, (1)H NMR data suggest that the ethyl esters form inclusion complexes with β-cyclodextrin. Compaction of other, commercially available, omega-3 powders was performed as a comparison and deemed unsuccessful., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

This work describes a simple, sensitive and fast liquid chromatographic method using ultraviolet (UV) detection for the quantitation of Captisol™ (sulfobutyl ether-β-cyclodextrin, SBE-β-CD) in Vestipitant (GW597599) IV formulation. The chromatographic system consists of a cyano-modified silica stationary phase column with 0.5mM copper(II) acetate in 50/50 (v/v) water/acetonitrile and 0.05% (v/v) of trifluoroacetic acid as the mobile phase. Due to the fact that SBE-β-CD does not possess a chromophore suitable for UV detection, copper(II) acetate is used as a detection reagent. At low pH copper(II) acetate interacts with SBE-β-CD and produces mixed copper(II) [Cu(2+)] chelate and copper(II) mono acetate [CuOAc(+)] complexes, while displacing sodium ions [Na(+)] from the sulfobutyl ether (SBE) group. The copper(II)-SBE-β-CD interaction has optical properties that allow its detection by UV. This novel method is highly reproducible and reliable for accurate quantitation of SBE-β-CD content in the Vestipitant IV solution, and in the solution without the Vestipitant matrix., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The enantiomers of asenapine maleate (ASN), a novel antipsychotic against schizophrenia and mania with bipolar I disorder have been separated by cyclodextrin (CD) modified capillary zone electrophoresis for the first time. 15 different CDs were screened as complexing agents and chiral selectors, investigating the stability of the inclusion complexes and their enantiodiscriminating capacities. Although initially, none of the applied chiral selectors gave baseline separation, β-CD proved to be the most effective chiral selector. In order to improve resolution, an orthogonal experimental design was employed, altering the concentration of background electrolyte, organic modifier, pH, capillary temperature and applied voltage in a multivariate manner. The developed method (160 mM TRIS-acetate buffer pH 3.5, 7 mM β-CD, at 20 °C, applying 15 kV) was successful for baseline separation of ASN enantiomers (R(s)=2.40±0.04). Our method was validated according to ICH guidelines and proved to be sensitive, linear, accurate and precise for the chiral separation of ASN. Properties of the inclusion complexes, such as stoichiometry, atomic level intermolecular host-guest connections are proposed on the basis of ROESY NMR measurement, ESI-MS spectrometry and molecular modeling studies. It was found that the ASN-β-CD complex is of 1:1 composition, and either of the aromatic rings can be accommodated in the β-CD cavity., (Copyright © 2015 Elsevier B.V. All rights reserved.)

A novel continuous spectrophotometric assay to measure the activity of the debranching enzyme and α-amylase has been developed. The assay mixture comprises the debranching enzyme (GlgX from Escherichia coli) or α-amylase (PPA from porcine pancreas), a reducing end-specific α-glucosidase (MalZ), maltodextrin-branched β-cyclodextrin (Glcn-β-CD) as the substrate, and the glucose oxidase/peroxidase system (GOPOD). Due to its high reducing end specificity, the branch chains of the substrates are not hydrolyzed by MalZ. After hydrolysis by GlgX or PPA, the released maltodextrins are immediately hydrolyzed into glucose from the reducing end by MalZ, whose concentration is continuously measured by GOPOD at 510 nm in a thermostat spectrophotometer. The kinetic constants determined for GlgX (Km = 0.66 ± 0.02 mM and kcat = 76.7 ± 1.5 s(-1)) are within a reasonable range compared with those measured using high-performance anion-exchange chromatography (HPAEC). The assay procedure is convenient and sensitive, and it requires lower concentrations of enzymes and substrate compared with dinitrosalicylic acid (DNS) and HPAEC analysis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

A new strategy for construction an electrochemical biosensor for Hg(2+) analysis with extremely high sensitivity was proposed based on "T-Hg(2+)-T" coordination by aptamers and "gate-controlled" amplification by switch of the channels of the probe. SH-β-cyclodextrin was self-assembled on the gold electrode to form an orderly arranged molecularly layer with interspaces among β-CDs; thionine labeled aptamer was then linked on the assembled β-CD. When Hg(2+) was added, the aptamer combined with Hg(2+) and formed "T-Hg(2+)-T" structure, which caused the aptamer folded and the labeled thionine covered the interspaces to block off the channel for probe entrance. The oxidative current of probe decreased, which provide the basis for the determination of Hg(2+). With the gate-controlled amplification, the changes of trace amounts of Hg(2+) will produce great changes of the probe current. The sensor exhibited significantly higher sensitivity with a detection limit of 5.0×10(-15) mol/L, which is lower than other reported methods., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Phytoglycogen (PG), a dendrimer-like glucan particulate, has a much higher dispersed molecular density than amylopectin (AP). In this study, β-amylase was used to investigate the effect of high molecular density of PG on its susceptibility to enzymatic hydrolysis. AP and PG reached the limit of β-amylolysis at 20 and 480 min, respectively, suggesting a much higher resistance of PG to β-amylase. The majority of PG β-amylolysis occurred in the initial 2 min, followed by a slow progression that implied low accessibility of internal particulate portion to enzyme. The chain length profile of PG β-limit dextrin showed only one population of long chains, indicating the absence of branch clusters with PG. At the limit of β-amylolysis, a substantial decrease in the molar mass was observed for both PG and AP, whereas only a slight reduction in the Z-average root mean square radius was observed for PG (from 24.5 to 23.1 nm) compared to that of AP (from 91.1 to 69.6 nm)., (Copyright © 2015. Published by Elsevier Ltd.)

The present research deals with the multi-collection of the most important sesquiterpene alcohols belonging to sandalwood essential oil, as reported by the international regulations: (Z)-α-santalol, (Z)-α-trans bergamotol, (Z)-β-santalol, epi-(Z)-β-santalol, α-bisabolol, (Z)-lanceol, and (Z)-nuciferol. A versatile multidimensional preparative system, based on the hyphenation of liquid and gas chromatography techniques, was operated in the LC-GC-GC-prep or GC-GC-GC-prep configuration, depending on the concentration to be collected from the sample, without any hardware or software modification. The system was equipped with a silica LC column in combination with polyethylene glycol-poly(5% diphenyl/95% dimethylsiloxane)-medium polarity ionic liquid or β-cyclodextrin based GC stationary phases. The GC-GC-GC-prep configuration was exploited for the collection of four components, by using a conventional split/splitless injector, while the LC-GC-GC-prep approach was applied for three low abundant components (<5%), in order to increase the quantity collected within a single run, by the LC injection of a high sample amount. All target compounds, whose determination is hampered by the unavailability of commercial standards, were collected at milligram levels and with a high degree of purity (>87%)., (Copyright © 2015 Elsevier B.V. All rights reserved.)

A simple HPLC-ELSD method was developed for the separation and quantification of native cyclodextrins. The technique was validated in the presence of two interfering matrices composed of byproducts from the cyclization medium. A fast separation of the compounds was achieved (in <20min) using a NUCLEODUR(®) C18 Pyramid column (150mm×4.6mm; particle size 5μm) at 30°C. The analytes were eluted using a linear gradient of acetonitrile and water containing 1% (v/v) of acetic acid at a flow rate of 0.3mL/min. Validation results showed that the method was accurate (93-110%) and selective. The precision was ≤5.7% for a hydrolyzed starch blank matrix spiked with cyclodextrins, and ≤6.2% for a blank matrix composed of a mixture of dextrin and glucose spiked with cyclodextrins. The limit of quantification was 0.05g/L for alpha- and 0.06g/L for beta- and gamma-cyclodextrins. The new HPLC-ELSD method could accurately quantify the three cyclodextrins directly in a cyclization medium, without pretreatment of the samples., (Copyright © 2015 Elsevier B.V. All rights reserved.)

A fully automated solid phase microextraction (SPME) depletion method was developed to study the partition coefficient of organic compound between complex matrix and water sample. The SPME depletion process was conducted by pre-loading the fiber with a specific amount of organic compounds from a proposed standard gas generation vial, and then desorbing the fiber into the targeted samples. Based on the proposed method, the partition coefficients (Kmatrix) of 4 polyaromatic hydrocarbons (PAHs) between humic acid (HA)/hydroxypropyl-β-cyclodextrin (β-HPCD) and aqueous sample were determined. The results showed that the logKmatrix of 4 PAHs with HA and β-HPCD ranged from 3.19 to 4.08, and 2.45 to 3.15, respectively. In addition, the logKmatrix values decreased about 0.12-0.27 log units for different PAHs for every 10°C increase in temperature. The effect of temperature on the partition coefficient followed van't Hoff plot, and the partition coefficient at any temperature can be predicted based on the plot. Furthermore, the proposed method was applied for the real biological fluid analysis. The partition coefficients of 6 PAHs between the complex matrices in the fetal bovine serum and water were determined, and compared to ones obtained from SPME extraction method. The result demonstrated that the proposed method can be applied to determine the sorption coefficients of hydrophobic compounds between complex matrix and water in a variety of samples., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: The aim of this study was to prove the capability of β-cyclodextrin (β-CD) to interact with some representative molecules responsible to cause body malodour, such as carboxylic acids, thiols and steroids, present in sweat and body secretions., Methods: The association constants in guest-CD were determined by (1) H-NMR spectroscopy for thiols and steroids such as 3-mercapto-1-hexanol, androstenone, androstenol and androsterone, and pH-potentiometric titration for acetic acid, l(+) lactic acid, isobutyric acid, isovaleric acid and 3-hydroxy-3-methyl-hexanoic acid., Results: All considered systems are able to interact with relatively weak association constants with β-cyclodextrin, in a 1 : 1 host-guest ratio., Conclusion: From these findings, it is possible to conclude that β-CD is capable to interact with different components present in the sweat and body secretion, forming inclusion complexes. For this reason, β-CD could be a component of body care formulations, such as deodorants., (© 2015 Society of Cosmetic Scientists and the Société Française de Cosmétologie.)

Quantification of 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD) is not yet described in United States Pharmacopeia (USP) and European Pharmacopeia (EP). A useful quality control tool is therefore needed for the specific quantification in finished liquid pharmaceutical products, especially for formulations containing 2-HP-β-CD as an active ingredient. A new technique is also mandatory for the development of future formulations in which 2-HP-β-CD concentration could influence the properties of these formulations. Here, we described the use of (1)H NMR for the rapid quantification of 2-HP-β-CD directly into pharmaceutical solutions without any extraction or separation steps. This technique was successfully applied to different pharmaceutical solutions comprising an i.v. solution (budesonide/2-HP-β-CD complex), an eye drop solution (Indocollyre®) and an oral solution (Sporanox®). Specificity, linearity, precision (repeatability and intermediate precision), trueness, limits of quantification (LOQs) and accuracy were used as validation criteria., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Introduction: Norfloxacin (NFX) is a broad spectrum antibiotic with low solubility and permeability, which is unstable on exposure to light and humidity., Objective: In this study, the mode of NFX inclusion into β-cyclodextrin complexes was evaluated and a complete physical, chemical and microbiological stability study of the inclusion complexes was carried out., Methods: Potentiometric titrations were performed to evaluate changes in the pKa of the NFX molecule due to the formation of an inclusion complex and NMR analysis demonstrated that the NFX molecule is included in the β-cyclodextrin cavity., Results: Inclusion complexes obtained by kneading followed by freeze-drying showed improved NFX stability compared with the isolated drug or the physical mixture. This method was effective in terms of protecting the drug from photodegradation and also avoiding hydrolysis. Differences between NFX and the complexes could be evidenced by thermal analysis, infrared spectroscopy and x-ray powder diffraction as well as by determining the solubility and drug content. The antimicrobial potency was also preserved on applying the promising method of kneading., Conclusion: The satisfactory stability indicates that the NFX/β-cyclodextrin complexes could be useful as an alternative to the existing NFX drug formulation.

The objective of the present work was to investigate the inclusion behavior of bendamustine (BM) with β-cyclodextrin and its hydrophilic derivatives (HP-β-CD and Epi-β-CD) for the enhancement of aqueous solubility, dissolution and bioavailability. The supramolecular binary complexes were prepared by three different methods, viz. physical mixture (PM), kneading (KND) and co-evaporation (COE). Phase-solubility study revealed the higher solubilizing and complexing ability of polymerized cyclodextrin (Ks = 645 M(-1)) than parent cyclodextrin (Ks = 43 M(-1)) and chemically derived cyclodextrin (Ks = 100 M(-1)). Meanwhile, the solubility of BM was significantly enhanced in phosphate buffer of pH 6.8, which was 24.5 folds greater compared with the phosphate buffer pH 4.5 and four times greater than aqueous medium. The dissolution efficiency was found to be highest for BM: Epi-β-CD complex (87%) compared to BM: HP-β-CD complex (84%), BM: β-CD (79%) and pure drug (20%). In-vivo pharmacokinetic study revealed that the bioavailability of BM was enhanced 2.55 times on complexation with Epi-β-CD using KND method. The t1/2 of BM was increased from 34.2 min to approximately 75.7 min, allowing the absorption for longer time. The order of increase in solubility, dissolution and bioavailability of BM was KND > COE > PM > pure drug. Thus, the strategy of host-guest inclusion was very effective and could be successfully used in the development of suitable pharmaceutical dosage form with enhanced therapeutic activity.

The integration of nanotechnology with mass spectrometry for sensitive and selective detection of molecules is a hot/important field of research. Synthesis of graphene (G) coated with mesoporous silica (SiO2, G@SiO2) for mass spectrometric application has been demonstrated. For the first time, we proposed the significant role of surfactant that used during the synthesis of mesorporous silicate (SiO2) in mass spectrometry. It was noticed that G could initiate SiO2 via surfactants which work as initiators for further ionization. The porosity of SiO2 trapped the analytes that was released and ionized with the surfactant fragments. Undoubtedly, strong background interferences were present in the case of organic matrix, which greatly obscured the detection of low molecular weight compounds. G@SiO2 nanocomposite affords several advantages, such as the ability to detect small molecules (<500Da), high sample localization through silica mesoporosity, and high ionization efficiency over than G or conventional matrices. The high performance of G@SiO2 is not only due to the large surface area but also due to high desorption/ionization efficiency of inevitably surfactant (cetyltrimethylammonium chloride, CATB). Unlike the conventional MALDI-MS, the G@SiO2-MS is capable of generating multiply charged polysaccharides. The present method was validated to detect surfactants with low limits of detection., (Copyright © 2014 Elsevier B.V. All rights reserved.)

We present the application of nanogels with high functional β-cyclodextrin (β-CD) content as new and versatile method for the modification and protection of textiles. The complexation potential of covalently embedded β-CD in nanogels is demonstrated for the common insecticide permethrin in aqueous environment. It is shown that permethrin containing β-CD nanogels can be applied easily, homogeneously and safely on keratin fibers like wool fabrics and human hairs. The permethrin concentration on fibers is directly controlled by the permethrin content in nanogels. We tested the permanence of permethrin on treated fibers with regard to washing and UV fastness. Our results show that permethrin complexed in nanogels is removed from the textile during washing, but that the complexation of permethrin by β-CD domains in the nanogels protects the active ingredient from UV degradation. Bioassay tests against the larvae of Tineola bisselliella and Anthrenocerus australis show that the activity of the ingredients does not decrease after complexation in β-CD gels and it results in protection of the wool fibers against degradation by the insect larvae.

A decontamination technique based in cyclodextrin extraction has been developed to eliminate nonylphenol (NP) and 16 polycyclic aromatic hydrocarbons (PAHs; the US Environmental Protection Agency priority pollutants list) from sewage sludge. In a first step, PAHs and NP were characterised in six sludges to determine contamination levels according to limit values proposed by the European Union Sludge Directive draft. There were few variations in the total PAHs content with levels of 1.88 to 3.05 mg kg(-1). Three-ring PAHs predominated, but fluoranthene and pyrene were also present. None of the sludge exceeded the PAHs limit proposed by the European Union's draft Directive. On the contrary, NP content in four of the six sludges was over the recommended limits of 50 mg kg(-1) for NP ethoxylates. With the aim of obtaining NP values below the concentration limits proposed to use the sewage sludge as agricultural amendments, a preliminary study using hydroxypropyl-β-cyclodextrin (HPBCD) extractions as a decontamination technique was carried out. About 90% of NP content was removed with only one extraction with HPBCD, whereas after three sequential extractions using an aqueous solution without HPBCD, the NP extraction percentage was less than 1%. Simultaneously, PAHs extraction percentages obtained with HPBCD were also much higher than when aqueous solution was used, especially in the case of two- and three-ring PAHs. Finally, the potential environmental hazard of HPBCD leachates to aquatic organisms (Daphnia magna) was tested. These results indicate that the treatment of sewage sludge with cyclodextrin could allow their safe use as fertiliser in agriculture.

Polycyclic aromatic hydrocarbons (PAHs) are among the most targeted contaminants by international regulatory institutions. There is thus a need for fast, selective and sensitive analytical methods to quantify these compounds at trace levels in complex samples. This article focuses on the optimization by means of an experimental design of a CE method with laser-induced fluorescence detection for the fast simultaneous separation of 8 heavy PAHs among food and environmental priority pollutants: benzo(a)pyrene, benzo(a)anthracene, chrysene, benzo(b)fluoranthene, dibenzo(a,h)anthracene, indeno(1,2,3-cd)pyrene, benzo(k)fluoranthene, and benzo(ghi)perylene. In this method, capillary zone electrophoresis with a mixture of an anionic sulfobutyl ether-β-cyclodextrin (SBE-β-CD) and a neutral methyl-β-cyclodextrin (Me-β-CD) was used to separate PAHs, on the basis of their differential distribution between the two CDs. First, the factors most affecting PAH electrophoretic behavior were identified: SBE-β-CD and Me-β-CD concentrations and percentage of methanol added to the background electrolyte. Then, a response surface strategy using a central composite design was carried out to model the effects of the selected factors on the normalized migration times. To optimize the separation, desirability functions were applied on modeled responses: normalized migration time differences between peak end and peak start of two consecutive peaks, and overall analysis time. From the model, predicted optimum conditions were experimentally validated and full resolution of all 8 PAHs was achieved in less than 7min using a borate buffer composed of 5.3mM SBE-β-CD, 21.5mM Me-β-CD and 10.3% MeOH. This CE separation method was successfully applied to real edible oil analysis., (Copyright © 2013 Elsevier B.V. All rights reserved.)

We describe a novel method for rapid and ultrasensitive detection of intact glycoproteins without enzymatic pretreatment which was commonly used in proteomic research. This method is based on using gold nanoparticle (AuNP) as signal tag in laser desorption/ionization mass spectrometry (LDI-MS) analysis combined with boronic acid assisted isolation strategy. Briefly speaking, target glycoproteins were firstly isolated from sample solution with boronic acid functionalized magnetic microparticles, and then the surface modified gold nanoparticles were added to covalently bind to the glycoproteins. After that, these AuNP tagged glycoproteins were eluted from magnetic microparticles and applied to LDI-MS analysis. The mass signal of AuNP rather than that of glycoprotein was detected and recorded in this strategy. Through data processing of different standard glycoproteins, we have demonstrated that the signal of AuNP could be used to quantitatively represent glycoprotein. This method allows femtomolar detection of intact glycoproteins. We believe that the successful validation of this method on three different kinds of glycoproteins suggests the potential use for tracking trace amount of target glycoproteins in real biological samples in the near future., (Copyright © 2013 Elsevier B.V. All rights reserved.)

A modular labeling strategy was presented for electrochemical immunoassay via supramolecular host-guest interaction between β-cyclodextrin (β-CD) and adamantine (ADA). An ADA-labeled antibody (ADA-Ab) was synthesized via amidation, and the number of ADA moieties loaded on a single antibody was calculated to be ~7. The β-CD-functionalized gold-palladium bimetallic nanoparticles (AuPd-CD) were synthesized in aqueous solution via metal-S chemistry and characterized with transmission electron microscopy and X-ray photoelectron spectra. After the ADA-Ab was bound to the antigen-modified electrode surface with a competitive immunoreaction, AuPd-CD as a signal tag was immobilized onto the immunosensor by a host-guest interaction, leading to a large loading of AuPd nanoparticles. The highly efficient electrocatalysis by AuPd nanoparticles for NaBH4 oxidation produced an ultrasensitive response to chloramphenicol as a model of a small molecule antigen. The immunoassay method showed a wide linear range from 50 pg/mL to 50 μg/mL and a detection limit of 4.6 pg/mL. The specific recognition of antigen by antibody resulted in good selectivity for the proposed method. The host-guest interaction strategy provided a universal labeling approach for the ultrasensitive detection of small molecule targets.

Multiwalled carbon nanotubes are evaluated here as solid phase extraction (SPE) sorbent aiming to (±)-chlorpheniramine (CPA) enantioresolution with fluorimetric detection. β-cyclodextrin (CD) was added to the racemate and solutions with HCl and sodium dodecyl sulfate (SDS) in different proportions were assayed as eluents to achieve the separation between both enantiomers. The overall methodology involved a flow injection (FI) strategy enabling high sample throughput and low reagents consumption making it suitable for drug routine quality control. An adequate enantioresolution (2.08) with satisfactory responses for both (R)-CPA (peak area=285) and (S)-CPA (peak area=380) was achieved applying the proposed FI-SPE strategy under the optimized conditions [β-CD] = 1.0 mmol L(-1), [HCl] = 1.0 × 10(-2) mol L(-1), [SDS] = 4.0 × 10(-4) mol L(-1) and eluent flow rate = 8.0 rpm., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The enantioseparation of acidic and neutral compounds can be successfully achieved in capillary electrophoresis (CE) using dual cyclodextrin (CD) systems. This chapter describes how to separate the enantiomers of acidic or neutral substances using dual CD systems made up of a negatively charged CD derivative, i.e., sulfobutyl-β-CD (SB-β-CD) or carboxymethyl-β-CD (CM-β-CD), in combination with a neutral one, namely, heptakis(2,3,6-tri-O-methyl)-β-CD (TM-β-CD). An acidic compound (carprofen) and a weakly acidic drug (pentobarbital) were selected as model compounds.

The enantioseparation of acidic and basic compounds can be successfully achieved in nonaqueous capillary electrophoresis using single-isomer charged β-cyclodextrin (β-CD) derivatives of opposite charge to that of the analytes. This chapter describes how to separate the enantiomers of three basic substances selected as model compounds, i.e., alprenolol, bupranolol, and terbutaline, using the negatively charged heptakis(2,3-di-O-acetyl-6-O-sulfo)-β-CD. The enantiomers of three acidic drugs (tiaprofenic acid, suprofen, and flurbiprofen) are resolved using a monosubstituted amino β-CD derivative, namely, 6-monodeoxy-6-mono(3-hydroxy)propylamino-β-CD.

An up-to-date overview of thin-layer chromatography (TLC) techniques for chiral separations of various significant and/or recent examples of enantioresolutions is reported. Furthermore, examples for chiral separations obtained on achiral commercially available C18 TLC plates are described in detail. These include the enantioseparation of methylthiohydantoin-phenylalanine and methylthiohydantoin-tyrosine using hydroxyethyl-β-cyclodextrin as mobile phase additive and the separation of the enantiomers of warfarin and p-chlorowarfarin using bovine serum albumin as mobile phase additive.

The aim of this work was to investigate the potential synergistic effect of water-soluble polymers (hypromellose, HPMC and polyvinylpyrrolidone, PVP) on zaleplon (ZAL) complexation with parent β-cyclodextrin (βCD) and its randomly methylated derivative (RAMEB) in solution and in solid state. The addition of HPMC to the complexation medium improved ZAL complexation and solubilization with RAMEB (K(ZAL/RAMEB)=156±5M(-1) and K(ZAL/RAMEB/HPMC)=189±8M(-1); p<0.01), while such effect was not observed for βCD (K(ZAL/βCD)=112±2M(-1) and K(ZAL/βCD/HPMC)=119±8M(-1); p>0.05). Although PVP increased the ZAL aqueous solubility from 0.22 to 0.27mg/mL, it did not show any synergistic effects on ZAL solubilization with the cyclodextrins tested. Binary and ternary systems of ZAL with βCD, RAMEB and HPMC were prepared by spray-drying. Differential scanning calorimetry, X-ray powder diffraction and scanning electron microscopy demonstrated a partial ZAL amorphization in spray-dried binary and ternary systems with βCD, while the drug was completely amorphous in all samples with RAMEB. Furthermore, inclusion complex formation in all systems prepared was confirmed by solid-state NMR spectroscopy. The in vitro dissolution rate followed the rank order ZAL/RAMEB/HPMC>ZAL/RAMEB=ZAL/βCD/HPMC>ZAL/βCD≫ZAL, clearly demonstrating the superior performance of RAMEB on ZAL complexation in the solid state and its synergistic effect with HPMC on drug solubility. Surprisingly, when loaded into tablets made with insoluble microcrystalline cellulose, RAMEB complexes had no positive effect on drug dissolution, because HPMC and RAMEB acted as a binders inside the tablets, prolonging their disintegration. Oppositely, the formulation with mannitol, a soluble excipient, containing a ternary RAMEB system, released the complete drug-dose in only 5min, clearly demonstrating its suitability for the development of immediate-release oral formulation of ZAL., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objectives: The aim of this study was to determine if spray-drying could successfully produce microparticles containing the model protein trypsin in a form suitable for inhalation., Methods: Trypsin was spray-dried with raffinose from a methanol : n-butyl acetate solvent system (MeOH : BA). The solvent system was then adjusted to include water, and trypsin was co-spray-dried with raffinose, trehalose or hydroxpropyl-β-cyclodextrin. The spray-dried products were characterised by SEM, XRD, DSC, TGA and FTIR. Protein biological activity and in-vitro deposition of trypsin : excipient nanoporous/nanoparticulate microparticles (NPMPs) was also assessed., Key Findings: The inclusion of water in a MeOH : BA solvent system allowed for the successful production of NPMPs of trypsin : excipient by spray-drying. Trypsin formulated as trypsin : excipient NPMPs retained biological activity on processing and showed no deterioration in activity or morphological characteristics when stored with desiccant at either 4 or 25°C. Hydroxpropyl-β-cyclodextrin showed advantages over the sugars in terms of producing powders with appropriate density and with greater physical stability under high-humidity conditions. Fine particle fractions of between 41 and 45% were determined for trypsin : excipient NPMPs., Conclusions: NPMPs of trypsin : excipient systems can be produced by spray-drying by adjustment of the solvent system to allow for adequate solubility of trypsin., (© 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.)