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Laundry wastewater is a significant source of nonylphenol ethoxylate (NPEO) at wastewater treatment plants, where its breakdown forms persistent nonylphenol (NP). NP poses risks as an endocrine disruptor in wildlife and humans. This study investigates the degradation of NPEO and COD in industrial laundry wastewater (LWW) using a two-stage process combining ultrafiltration (UF) and electro-oxidation (EO). UF was used to remove suspended solids, while soluble COD (COD 0  = 239 ± 6 mg.L -1 ) and NPEO (NPEO 0  = 341 ± 8 μg.L -1 ) were oxidized by the EO process. Different operating parameters were studied such as current density, electrolysis time, type of cathode and supporting electrolyte concentration. Using an experimental design methodology, the optimal conditions for COD and NPEO 3-17 degradation were recorded. This included achieving 97% degradation of NPEO 3-17 and 61% degradation of COD, with a total operating cost of 3.65 USD·m -3 . These optimal conditions were recorded at a current density of 15 mA cm -2 for a 120-min reaction period in the presence of 4 g·Na 2 SO 4 L -1 using a graphite cathode. The EO process allowed for reaching the guidelines required for water reuse (NPEO <200 μg.L -1 , COD <100 mg.L -1 ) in the initial laundry washing cycles. Furthermore, our results demonstrate that both NP and NPEO compounds, including higher and shorter ethoxylate chains (NPEO 3-17 ), were effectively degraded during the EO process, with removal efficiencies between 94% and 98%. This confirms the EO process's capability to effectively degrade NP, the by-product of NPEO breakdown., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Patrick Drogui reports financial support was provided by National Sciences and Engineering Research Council of Canada. Patrick Drogui reports financial support was provided by CREATE TEDGIEER program. Patrick Drogui reports financial support was provided by Group VEOS. If there are other authors, they 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 © 2024 Elsevier Ltd. All rights reserved.)

Manufacturing processes in semiconductor and photonics industries involve the use of a significant amount of organic solvents. Recycle and reuse of these solvents produce distillate residues and require treatment before being discharged. This study aimed to evaluate the performance of the biological treatment system in a full-scale wastewater treatment plant that treats wastewater containing distillate residues from the recycling of electronic chemicals. Batch experiments were conducted to investigate the optimal operational conditions for the full-scale wastewater treatment plant. To achieve good nitrogen removal efficiency with effluent ammonia and nitrate concentrations below 20 mg N/L and 50 mg N/L, respectively, it was suggested to control the ammonia concentration and pH of the influent below 500 mg N/L and 8.0, respectively. In addition, the biodegradability of N-methylpyrrolidone, diethylene glycol monobutyl ether, and cyclopentanone distillate residues from the electronic chemicals manufacturing process were evaluated under aerobic, anoxic, and anaerobic conditions. N-methylpyrrolidone and cyclopentanone distillate residues were suggested to be treated under anoxic condition. However, substrate inhibition occurred when using cyclopentanone distillate residue as a carbon source with chemical oxygen demand (COD) levels higher than 866 mg/L and nitrate levels higher than 415 mg N/L. Under aerobic condition, the COD from both N-methylpyrrolidone and cyclopentanone distillate residues could be easily degraded. Nevertheless, a negative effect on nitrification was observed, with a prolonged lag time for ammonia oxidation as the initial COD concentration increased. The specific ammonia oxidation rate and nitrate production rate decreased under high COD concentration contributed by N-methylpyrrolidone and cyclopentanone distillate residues. Furthermore, the biodegradability of diethylene glycol monobutyl ether distillate residue was found to be low under aerobic, anoxic, and anaerobic conditions. With respect to the abundance of nitrogen removal microorganisms in the wastewater treatment plant, results showed that Comammox may have an advantage over ammonia oxidizing bacteria under high pH conditions. In addition, Comammox may have higher resistance to environmental changes. Dominance of Comammox over ammonia oxidizing bacteria under high ammonia condition was first reported in this study., 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 © 2024. Published by Elsevier Ltd.)

Eucalyptus was pretreated with diethylene glycol catalyzed by 0.02 mol/L CrCl 3 for 10 min, resulting in 91 % delignification and 98 % cellulose recovery, with trace fermentation inhibitors generated. After the mild pretreatment, the accessibility and affinity of cellulase to eucalyptus was enhanced, especially since enzyme adsorption rate increased by 1.6-fold. Therefore, glucose yield of pretreated eucalyptus was 7.9-fold higher than that of untreated eucalyptus after hydrolyzed 48 h, in which the maximum glucose concentration reached 62 g/L from eucalyptus by adding Tween 80. According to the characterization analysis, the structure of the eucalyptus lignin-carbohydrate complexes structure was destroyed during the pretreatment, while lignin fragments was likely reacted with diethylene glycol to form the stabilized aromatic ethers. Moreover, the extracted Deg-lignin exhibited better performances than commercial alkali lignin such as higher fluorescence intensity, less negative surface charge, and lower particle size. The mild pretreatment method with diethylene glycol and CrCl 3 provided a promising approach for co-production of fermentable sugars and high activity lignin from lignocellulosic biomass., 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 © 2024 Elsevier B.V. All rights reserved.)

The widely-used surfactant Nonylphenol Ethoxylate (NPEO) produces endocrine-disrupting compounds during biodegradation, with these byproducts being more harmful than untreated NPEO. This study investigates the effectiveness of a Fluidized Bed Reactor (FBR) in reducing the production of 4-Nonylphenol (4-NP) during the biodegradation of NPEO. Two identical FBR filled with sand were used to assess the NPEO degradation and to enhance the microbial consortia capable of breaking down the complex byproducts, ethanol and fumarate were introduced as co-substrates. Our findings demonstrate the significant potential of the FBR, especially when coupled with fumarate, for enhancing the surfactant degradation. It outperforms the efficiency achieved with ethanol as the primary electron donor, albeit with a higher rate of byproduct production. Microbial community taxonomy and metabolic prediction revealed the high abundance of Geobacter (1.51-31.71%) and Methanobacterium (1.08-13.81%) in non-conductive sand. This may hint a new metabolic interaction and expand our understanding of Direct Interspecies Electron Transfer (DIET) in bioreactors applied to micropollutants degradation. Such an intricate relationship between facultative and anaerobes working together to simultaneously biodegrade the ethoxy and alkyl chains presents a new perspective on NPEO degradation and can potentially be extended to other micropollutants., 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 © 2024. Published by Elsevier Ltd.)

Detergents are highly produced pollutants with environmental problems like foam generation and toxic effects in biota. Nonylphenol ethoxylates (NPEs) are efficient, economical, and versatile surfactants, used in detergents for more than 40 years due to their detergency capacity. In the environment, NPE biodegrades into the metabolite nonylphenol (NP), classified as an endocrine disruptor. The identification and quantification of 4-NP in a designed detergent and 30 commercially available detergents were performed to prove the degradation of NPE into 4-NP during storage time. This investigation introduces the first evidence of NPE degradation during storage in commercially available detergents, demonstrating a novel exposure pathway in humans that has not been explored before, representing potential human health risks. Therefore, simple, easy, low-cost, and available approaches to remove and substitute NP is paramount. Alkyl polyglucoside (APG) was assessed as a substitute, and the feasibility of this substitution was proven according to physical and chemical properties, cleaning performance, and antimicrobial properties. NPE substitution in detergents is demonstrated as a viable strategy to minimize exposure risks in humans and the environment., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In the present work, we described the preparation and characterization of the micelles based on amphiphilic poly(ε-caprolactone- block -ethylene glycol) block copolymer ( PCL- b -PEG ) loaded with non-symmetric [Pt(C^N*N'^C')] complex ( Pt1 ) (where C^N*N'^C': 6-(phenyl(6-(thiophene-2-yl)pyridin-2-yl)amino)-2-(tyophene-2-yl)nicotinate). The obtained nanospecies displayed the ignition of near-infrared (NIR) phosphorescence upon an increase in the content of the platinum complexes in the micelles, which acted as the major emission component at 12 wt.% of Pt1 . Emergence of the NIR band at 780 nm was also accompanied by a 3-fold growth of the quantum yield and an increase in the two-photon absorption cross-section that reached the value of 450 GM. Both effects are believed to be the result of progressive platinum complex aggregation inside hydrophobic poly(caprolactone) cores of block copolymer micelles, which has been ascribed to aggregation induced emission (AIE). The resulting phosphorescent ( Pt1@PCL- b -PEG ) micelles demonstrated pronounced sensitivity towards molecular oxygen, the key intracellular bioanalyte. The detailed photophysical analysis of the AIE phenomena revealed that the NIR emission most probably occurred due to the excimeric excited state of the 3 MMLCT character. Evaluation of the Pt1@PCL- b -PEG efficacy as a lifetime intracellular oxygen biosensor carried out in CHO-K1 live cells demonstrated the linear response of the probe emission lifetime towards this analyte accompanied by a pronounced influence of serum albumin on the lifetime response. Nevertheless, Pt1@PCL- b -PEG can serve as a semi-quantitative lifetime oxygen nanosensor. The key result of this study consists of the demonstration of an alternative approach for the preparation of NIR biosensors by taking advantage of in situ generation of NIR emission due to the nanoconfined aggregation of Pt (II) complexes inside the micellar nanocarriers.

Recent studies have highlighted the benefit of repurposing oral erlotinib (ERL) treatment in some rare skin diseases such as Olmsted syndrome. The use of a topical ERL skin treatment instead of the currently available ERL tablets may be appealing to treat skin disorders while reducing adverse systemic effects and exposure. A method to prepare 0.2% ERL cream, without resorting to a pure active pharmaceutical ingredient, was developed and the formulation was optimized to improve ERL stability over time. Erlotinib extraction from tablets was incomplete with Transcutol, whereas dimethyl sulfoxide (DMSO) allowed 100% erlotinib recovery. During preliminary studies, ERL was shown to be sensitive to oxidation and acidic pH in solution and when added to selected creams (i.e., Excipial, Nourivan Antiox, Pentravan, and Versatile). The results also showed that use of DMSO (5% v / w ), neutral pH, as well as a topical agent containing antioxidant substances (Nourivan Antiox) were key factors to maintain the initial erlotinib concentration. The proposed ERL cream formulation at neutral pH contains a homogeneous amount of ERL and is stable for at least 42 days at room temperature in Nourivan cream with antioxidant properties.

Between 293.2 and 313.2 K and at 0.1 MPa, the solubility of the weak base, cinnarizine (CNZ) (3), in various {Transcutol-P (TP) (1) + water (2)} combinations is reported. The Hansen solubility parameters (HSP) of CNZ and various {(TP) (1) + water (2)} mixtures free of CNZ were also predicted using HSPiP software. Five distinct cosolvency-based mathematical models were used to link the experimentally determined solubility data of CNZ. The solubility of CNZ in mole fraction was increased with elevated temperature and TP mass fraction in {(TP) (1) + water (2)} combinations. The maximum solubility of CNZ in mole fraction was achieved in neat TP (5.83 × 10 -2 at 313.2 K) followed by the minimum in neat water (3.91 × 10 -8 at 293.2 K). The values of mean percent deviation ( MPD ) were estimated as 2.27%, 5.15%, 27.76%, 1.24% and 1.52% for the "Apelblat, van't Hoff, Yalkowsky-Roseman, Jouyban-Acree, and Jouyban-Acree-van't Hoff models", respectively, indicating good correlations. The HSP value of CNZ was closed with that of neat TP, suggesting the maximum solubilization of CNZ in TP compared with neat water and other aqueous mixtures of TP and water. The outcomes of the apparent thermodynamic analysis revealed that CNZ dissolution was endothermic and entropy-driven in all of the {(TP) (1) + water (2)} systems investigated. For {(TP) (1) + water (2)} mixtures, the enthalpy-driven mechanism was determined to be the driven mechanism for CNZ solvation. TP has great potential for solubilizing the weak base, CNZ, in water, as demonstrated by these results.

Solidification of self-microemulsifying drug delivery systems (SMEDDS) is one of the major trends to promote the transformation of self-microemulsion technology into industrialization. Here, a preliminary curcumin SMEDDS formulation was constructed to improve the druggability of curcumin, through the determination of equilibrium solubility determination, self-emulsifying grading assessment, and pseudo-ternary phase diagrams drafting. Furthermore, the optimal curcumin SMEDDS formulation consisted of 10% Ethyl oleate, 57.82% Cremophor RH 40, and 32.18% Transcutol P was obtained by the simplex lattice design. Besides, curcumin solid self-microemulsifying drug delivery system (S-SMEDDS) was developed by the extrusion and spheronization process to achieve the solidification of SMEDDS. The formulation of curcumin S-SMEDDS pellets was screened by the single factor experiment and the process parameters were investigated using the orthogonal optimization method. Subsequently, curcumin S-SMEDDS pellets were evaluated by apparent morphology characterization, redispersibility study, drug release behavior, and pharmacokinetic evaluation. Results from the pharmacokinetic study in rabbits showed that the AUC 0-τ of the curcumin S-SMEDDS pellets and curcumin suspension were 5.91 ± 0.28 µg/mL·h and 2.05 ± 0.04 µg/mL·h, while the relative bioavailability was 289.30%. These studies demonstrated that S-SMEDDS pellets can be a promising strategy for curcumin industrialized outputs.

Accumulation of amyloid beta (Aβ) is one of the pathological hallmarks of Alzheimer's disease (AD), which can be visualized using [ 18 F]florbetapir positron emission tomography (PET). The aim of this study was to evaluate various parametric methods and to assess their test-retest (TRT) reliability. Two 90 min dynamic [ 18 F]florbetapir PET scans, including arterial sampling, were acquired ( n  = 8 AD patient, n  = 8 controls). The following parametric methods were used; (reference:cerebellum); Logan and spectral analysis (SA), receptor parametric mapping (RPM), simplified reference tissue model2 (SRTM2), reference Logan (rLogan) and standardized uptake value ratios (SUV r(50-70) ). BP ND +1, DVR, V T and SUVr were compared with corresponding estimates (V T or DVR) from the plasma input reversible two tissue compartmental (2T4k&#95;V B ) model with corresponding TRT values for 90-scan duration. RPM ( r 2  = 0.92; slope = 0.91), Logan ( r 2  = 0.95; slope = 0.84) and rLogan ( r 2  = 0.94; slope = 0.88), and SRTM2 ( r 2  = 0.91; slope = 0.83), SA ( r 2  = 0.91; slope = 0.88), SUVr ( r 2  = 0.84; slope = 1.16) correlated well with their 2T4k&#95;V B counterparts. RPM (controls: 1%, AD: 3%), rLogan (controls: 1%, AD: 3%) and SUV r(50-70) (controls: 3%, AD: 8%) showed an excellent TRT reliability. In conclusion, most parametric methods showed excellent performance for [ 18 F]florbetapir, but RPM and rLogan seem the methods of choice, combining the highest accuracy and best TRT reliability.

Numerous efforts to fabricate antimicrobial surfaces by simple yet universal protocols with high efficiency have attracted considerable interest but proved to be particularly challenging. Herein, we designed and fabricated a series of antimicrobial polymeric coatings with different functions from single to multiple mechanisms by selectively utilizing diethylene glycol diglycidyl ether (PEGDGE), polylysine, and poly[glycidylmethacrylate- co -3-(dimethyl(4-vinylbenzyl)ammonium)propyl sulfonate] (poly(GMA- co -DVBAPS)) via straightforward mussel-inspired codeposition techniques. Bactericidal polylysine endowed the modified surfaces with a high ability (∼90%) to kill attached bacteria, while PEGDGE components with unique surface hydration prevented bacterial adhesion, avoiding the initial biofilm formation. Moreover, excellent salt-responsive poly(GMA- co -DVBAPS) enabled reactant polymeric coatings to change chain conformations from shrinkable to stretchable state and subsequently release >90% attached bacteria when treated with NaCl solution, even after repeated cycles. Therefore, the obtained polymeric coatings, polydopamine/poly(GMA- co -DVBAPS) (PDA/PDV), polydopamine/polylysine/poly(GMA- co -DVBAPS) (PDA/l-PDV), and polydopamine/polylysine/poly(GMA- co -DVBAPS)/diethylene glycol diglycidyl ether (PDA/l-PDV-PEGDGE), controllably realized functions from single and dual to multiple antimicrobial mechanisms, as evidenced by long-term antifouling activity to bacteria, high bactericidal efficiency, and salt-responsive bacterial regeneration performance with several bacterial killing-release cycles. This study not only contributes to mussel-inspired chemistry for polymeric coatings with controllable functions but also provides a series of reliable and highly efficient antimicrobial surfaces for potential biomedical applications.

Poly((R)-3-hydroxybutyrate) (P(3HB)) is a polyester that is synthesized and accumulated in many prokaryotic cells. Recently, a new culture method for the secretion of the intracellularly synthesized (R)-3-hydroxybutyrate oligomer (3HBO) from recombinant Escherichia coli cells was developed. In this study, we attempted to produce microbial 3HBO capped with a diethylene glycol terminal (3HBO-DEG) as a macromonomer for polymeric materials. First, we prepared recombinant E. coli strains harboring genes encoding various polyhydroxyalkanoate (PHA) synthases (PhaC, PhaEC or PhaRC) that can incorporate chain transfer (CT) agents such as DEG into the polymer's terminal and generate CT end-capped oligomers. To this end, each strain was cultivated under DEG supplemental conditions, and the synthesis of 3HBO-DEG was confirmed. As a result, the highest secretory production of 3HBO-DEG was observed for the PHA synthase derived from Bacillus cereus YB-4 (PhaRC YB4 ). To evaluate the usability of the secreted 3HBO-DEG as a macromonomer, 3HBO-DEG was purified from the culture medium and polymerized with 4,4'-diphenylmethane diisocyanate as a spacer compound. Characterization of the polymeric products revealed that 3HBO-based polyurethane was successfully obtained and was a flexible and transparent noncrystalline polymer, unlike P(3HB). These results suggested that microbial 3HBO-DEG is a promising platform building block for synthesizing polyurethane and various other polymers., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A new, simple and rapid method for the quantitative determination of the antimicrobial preservative 2-phenoxyethanol, based on reverse phase ultra-high-performance liquid chromatography has been developed. The validation was performed according the ICH Q2 guideline "Validation of Analytical Procedures". The desired chromatographic separation was achieved on a Waters Symmetry C18 (150 × 4.6 mm, 5 μm) column using an isocratic elution, with detection at 270 nm wavelength. The mobile phase consisted of acetonitrile/water (55:45, v/v), pumped at a flow rate of 1 mL/min. The calibration curve and the analytical procedure are linear (r 2  = 0.999) from the concentration of 0.07 mg/mL to 1.1 mg/mL. The percent relative standard deviation for intra- and inter-day precision was <1%. The recovery of 2-phenoxyethanol in vaccines ranged between 96.5 and 100.60%. The limits of detection and quantitation were 1.3 × 10 -4 and 2.7 × 10 -4  mg/mL, respectively. The method was found to be robust by changing the column working temperature, the percentage of acetonitrile of the mobile phase and the flow rate. The validated method can be successfully and reliably used to quantify as well as to exclude presence of 2-phenoxyethanol preservative in marketed vaccines., (Copyright © 2021 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.)

Purpose: Ginkgolide B (GB) is a terpene lactone derivative of Ginkgo biloba that is believed to function in a neuroprotective manner ideal for treating Parkinson's disease (PD). Despite its promising therapeutic properties, GB has poor bioavailability following oral administration and cannot readily achieve sufficient exposure in treated patients, limiting its clinical application for the treatment of PD. In an effort to improve its efficacy, we utilized poly(ethylene glycol)-co-poly(ε-caprolactone) (PEG-PCL) nanoparticles as a means of encapsulating GB (GB-NPs). These NPs facilitated the sustained release of GB into the blood, thereby improving its ability to accumulate in the brain and to treat PD., Methods and Results: Using Madin-Darby canine kidney (MDCK) cells, we were able to confirm that these NPs could be taken into cells via multiple nonspecific mechanisms including micropinocytosis, clathrin-dependent endocytosis, and lipid raft/caveolae-mediated endocytosis. Once internalized, these NPs tended to accumulate in the endoplasmic reticulum and lysosomes. In zebrafish, we determined that these NPs were readily able to undergo transport across the chorion, gastrointestinal, blood-brain, and blood-retinal barriers. In a 1-methyl-4-phenylpyridinium ion (MPP + )-induced neuronal damage model system, we confirmed the neuroprotective potential of these NPs. Following oral administration to rats, GB-NPs exhibited more desirable pharmacokinetics than did free GB, achieving higher GB concentrations in both the brain and the blood. Using a murine PD model, we demonstrated that these GB-NPs achieved superior therapeutic efficacy and reduced toxicity relative to free GB., Conclusion: In conclusion, these results indicate that NPs encapsulation of GB can significantly improve its oral bioavailability, cerebral accumulation, and bioactivity via mediating its sustained release in vivo., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Zhao et al.)

Peroxidase mimics of nanoscale materials as alternatives to natural peroxidases have found widespread uses in biomedicine. Among various types of peroxidase mimics, platinum-group metal (PGM) nanocrystals have drawn considerable attention in recent years due to their superior properties. Particularly, PGM nanocrystals display high catalytic efficiencies, allow for facile surface modifications, and possess excellent stabilities. This feature article summarizes our recent work on development of PGM nanocrystals as peroxidase mimics and exploration of their applications in in vitro diagnostics. We begin with a brief introduction to controlled synthesis of PGM nanocrystals in solution phase. We then elaborate on a variety of physicochemical parameters that can be carefully tuned to optimize the peroxidase-like properties of PGM nanocrystals. Then, we highlight the applications of PGM nanocrystals in different in vitro diagnostic platforms. We conclude this article with personal perspectives on future research directions in this emerging field, where challenges and opportunities are remarked.

Background: Three different amyloid tracers labeled with 18-flourine have been introduced into clinical use. The leaflets of tracers indicate different visual criteria for PET reporting. In clinical practice, it is not yet ascertained whether these criteria are equivalent in terms of diagnostic accuracy or if anyone is better than another. We aimed to evaluate the inter and intra-rater variability of visual assessment of 18 F-Florbetapir PET/CT images among six independent readers with different clinical experience., Methods: We analyzed 252 PET/CT scans, visually assessed by each reader three times, applying independently the three different reading criteria proposed. Each reader evaluated the regional uptake specifying for each cortical region a numeric value of grading of positivity in order to assign a final score. At the end of each reading a level of confidence was determined by assigning a score from 0 (negative) to 4 (positive). After first reading, those cases in which the evaluations by two experienced readers did not match (discordant cases) were independently reevaluated merging all the three different visual interpretation criteria., Results: Good agreement was observed for visual interpretation among the six readers' confidence-level using independently the three visual reading criteria: ICC=0.83 (0.80-0.86) for 18 F-florbetapir, ICC=0.84 (0.81-0.87) for 18 F-florbetaben, and ICC=0.86 (0.83-0.88) for 18 F-flutemetamol reading. A good inter-rater agreement was observed for final-score too: ICC=0.74 (0.70-0.78) for 18 F-florbetapir; ICC=0.82 (0.79-0.85) for 18 F-florbetaben; ICC=0.84 (0.81-0.87) for 18 F-flutemetamol. Intra-rater agreement was good for final-score (from 0.76 to 0.90; P<0.001) and confidence-level (Spearman's rho from 0.89 to 1.00; P<0.001). Disagreement between the two experienced readers was observed in 22 of 252 cases (9%). The agreement converged over a second round of independent reading in 12 of 22 cases (54%), by merging all the criteria., Conclusions: All the criteria proposed are useful to determine the grading of positivity or negativity of amyloid deposition and their merging improves the diagnostic confidence and provides a better agreement.

Nanotherapeutics in cancer treatment are dominating global science and research, and have been recognized as the pioneering medical care regimen. Raloxifene (RLN) has been used for its anti-proliferative action on mammary tissue, however, it suffers from poor oral bioavailability. This investigation gives an account of the design and development of RLN-loaded nanostructured lipid carriers (RLN-NLCs) using a simple and scalable ultrasonication method for improved oral efficacy and limited offsite toxicity using Compritol ® 888 ATO as a solid lipid and Transcutol ® HP as a liquid lipid. In addition, the optimized RLN-NLCs were in the nanometric range (121 nm) with high % entrapment efficiency (%EE) (81%) for RLN, and were further freeze-dried in the presence of mannitol to enhance the stability of RLN-NLCs in the dry state for long-term use. Morphological observation under a transmission electron microscope and scanning electron microscope revealed the spherical smooth surface nanometric size of RLN-NLCs. Powder x-ray diffraction confirmed the encapsulation of RLN into the RLN-NLC's matrix with reduced crystallinity of the drug. The in vitro release study showed a burst release for an initial 4 h, and sustained release for up to 24 h. Furthermore, the RLN-NLCs showed higher cytotoxicity towards MCF-7 cells in vitro in comparison to RLN suspension, and an ex vivo intestinal permeation study demonstrated improved intestinal permeability of RLN-NLCs. Moreover, the in vivo pharmacokinetic study in female Wistar rats showed a 4.79-fold increment in oral bioavailability of RLN from RLN-NLCs compared to RLN suspension. Taken together, our results pave the way for a new nanotherapeutic approach towards breast cancer treatment.

With the increasing debate on sustainability, there is a strong market trend to formulate more sustainable products for topical application. Several studies emphasize the potential applications of natural, organic, or green chemistry-derived ingredients, but comparative studies between conventional ingredients and sustainable alternatives are lacking. This type of study is considered an excellent baseline and time-saving strategy for future studies. In addition, one of the main challenges of replacing ingredients by sustainable alternatives in topical vehicles is to maintain high-quality products. Thus, the main goal of this research study was to create a well-defined strategy supported by specific experimental data for the development of sustainable topical vehicles with high-quality standards. The study was designed to evaluate the effects of replacing conventional ingredients (e.g., hydrocarbons, silicones, and preservatives) by sustainable ones on the physical, chemical, and microbiological features of topical emulsions. Additionally, in vivo assessment studies were performed to evaluate the safety, biological efficacy, and sensorial aspects of the developed formulations. The results obtained showed that the replacement of ingredients by sustainable alternatives has an effective impact on the physicochemical and structural properties of the emulsions, mainly on their rheological behavior. However, using appropriate strategies for ingredient selection and rheological adjustment, it is possible to overcome some barriers created by the use of natural raw materials, thus developing appealing and high-quality sustainable topical vehicles.

Objective: Transcutol ® is a perfect solubilizer and an effective permeation enhancer of many active substances commonly used in cosmetics. Microemulsions due to the content of surfactant and co-surfactant could be also considered as chemical permeation enhancers that may support transdermal delivery of poorly water- soluble drugs. The purpose of this study was to investigate the effect of Transcutol ® and potential microemulsions on diffusion of poorly soluble indomethacin through an artificial membrane and excised rat skin., Methods: After drug solubilization in different enhancers, drug was dispersed in sodium alginate or carbopol gel used as dermal basis. For characterization of the microemulsions, the basic physico-chemical properties were determined. In vitro as well as ex vivo drug release was determined by vertical Franz cells., Results: Enhancing effect of the examined microemulsions was observed only in carbopol gel. There was an increase in cumulative drug amount released through synthetic membrane by 37.7-39.8% from the microemulsion formulation and 90.6% from Transcutol ® formulation within 6 h compared to the control samples. The differences between the permeation curves with or without the content of the enhancers were statistically significant ( p  < .05). Pearson correlation coefficients indicate a very high degree of dependence ( r  > 0.9) between in vitro and ex vivo drug release from all dermal vehicles used., Conclusion: It can be stated that Transcutol ® is the best solubilizer and also penetration enhancer from the examined, and therefore it seems to be effective excipient/solubilizer in topical IND formulation.

Investigation and identification of potential lipids for the manufacture of efavirenz loaded solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) was undertaken. Polymorphic modification and characteristics of the lipids with the best solubilising potential for efavirenz was explored using Fourier Transform Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC) and Wide-angle X-ray Scattering (WAXS). Lipid screening revealed that EFV is highly soluble in solid and liquid lipids, with glyceryl monostearate (GM) and Transcutol ® HP (THP) exhibiting the best solubilising potential for EFV. GM exists in a stable β-polymorphic modification prior to exposure to heat, but exists in an α-polymorphic modification following exposure to heat. However, it was established that the addition of THP to GM revealed the co-existence of the α- and β'-polymorphic modifications of the lipid. EFV (60% w/w ) exists in a crystalline state in a 70:30 mixture of GM and THP. Investigation of binary mixtures of EFV/GM and GM/THP, in addition to eutectic mixtures of EFV, GM and THP using FT-IR, DSC and WAXS revealed no potential interactions between EFV and the lipids selected for the production of the nanocarriers.

Double gloving of disposable gloves is now commonplace in healthcare settings when extra protection is needed against aqueous solutions and especially for antineoplastic drugs in isotonic aqueous media. In the present study, an ASTM F739 2.54 cm cell with closed-loop water collection without recirculation at 35 °C in a moving tray water bath was used to test the permeation of diethylene glycol mono-n-butyl ether (DGBE) through four types of disposable nitrile gloves that were singly and doubly layered in the permeation cell. Samples were taken over 8 hr for capillary gas chromatograph-mass spectrometer quantitation. The breakthrough time (t n ) at a permeation of 250 ng/cm 2 increased as thickness increased for single layers, but the steady-state permeation rates P s in µg/cm 2 /min did not always decrease with increasing thickness. The double-layer t n , P s and thickness were also more variable relative to a single layer. The thinnest glove with 80 [Formula: see text]m thickness showed a t n = 0-5 min whereas its double layer was 15-20 min. The thickest glove of 132 µm exhibited a t n = 10-15 min but its double layer was t n = 45-55 min. The adjusted double-layer average t n divided by the adjusted single-layer average t n was 4.0 ± 0.8. The adjusted average single-layer P s divided by the adjusted average double-layer P s was 3.5 ± 0.8. Other results showed that the average glove swelling was <10%; microscopic and leak testing indicated no penetration and reflectance infrared analysis also showed no chemical changes on the inside glove surfaces. Thus, the permeations were adjudged to obey Fick's First Law of Diffusion to allow calculation of diffusion coefficients D in cm 2 /min. The average single-layer D divided by the average double-layer D was 1.3 ± 0.2. Double gloving in the field is therefore also probably more protective than single gloving against DGBE for the four types of disposable nitrile gloves tested.

Objective: Artemisinin (ART) is a natural anti-malarial sesquiterpene lactone which has the ability to treat and activate the CLRN1 pathway to play a pivotal role in hearing loss and hair cell function. To investigate the therapeutic effect of ART in hearing loss induced by gentamicin (GM), an ART-loaded poly(ethylene glycol)-b-poly(ε-caprolactone) mPEG-PCL nanoparticle-based photosensitive hydrogel was developed and tested in this study., Materials and Methods: Artemisinin-loaded mPEG-PCL nanoparticles (mPEG-PCL-ART-NPs) were prepared by a double emulsion method and the formulation was optimized by an orthogonal experimental design. The particle size, zeta potential, morphology and in vitro dissolution of the mPEG-PCL-ART-NPs were well characterized. Biocompatibility of the mPEG-PCL-ART-NPs were tested on HeLa cells with an MTT assay. The photo-crosslinkable biodegradable gelatin methacrylate (GelMA) hydrogel was prepared and its physicochemical properties (such as substitution, photocrosslinking efficiency, cell viability morphology, mechanical and swelling properties) were evaluated. Finally, mPEG-PCL-ART-FITC-NPs, loaded mPEG-PCL-ART-NPs, and loaded mPEG-PCL-ART-NPs-GelMA hydrogels were fabricated and a GM toxicity-induced guinea pig ear damage model was established to determine the effectiveness of the materials on returning auditory function and cochlea pathomorphology., Results: The zeta potential of the mPEG-PCL-ART-NPs was about -38.64 ± 0.21 mV and the average size was 167.51 ± 1.87 nm with an encapsulation efficacy of 81.7 ± 1.46%. In vitro release studies showed that the mPEG-PCL-ART-NPs possessed a sustained-release effect and the MTT experiments showed good biocompatibility properties of the drug-loaded nanoparticles. The results indicated that the 5% GelMA with MA-4% hydrogel had a better crosslinking density and 3D structure for drug loading and drug delivery than controls. Skin penetration results showed that the mPEG-PCL-ART-NPs increased adhesive capacity and avoided fast diffusion in the skin. Most importantly, auditory brainstem response results indicated that the mPEG-PCL-ART-NPs-GelMA hydrogel alleviated hearing loss induced by GM., Conclusion: These results suggested that the presently fabricated mPEG-PCL-ART-NPs-GelMA hydrogels are promising formulations for the treatment of hearing loss induced by GM and lay the foundation for further clinical research of inner ear induction therapy., Competing Interests: The authors declare no conflicts of interest in this work., (© 2020 Li et al.)

Polymer microgels that respond in a range of neutral pH can be useful for the development of molecular imaging tools and drug-delivery carriers. Here, we describe a simple approach in developing microgels that undergo volume phase transitions and substantial nuclear magnetic resonance (NMR) relaxometric changes within a narrow pH range of 6.4 to 7.4. The pH-responsive microgels were synthesized using methacrylic acid and a series of ethylene glycol dimethacrylate cross-linkers with repeating units of ethylene glycol that range from one to four. NMR relaxometry demonstrated that the transverse relaxation time ( T 2 ) of a suspension containing microgels that were cross-linked with diethylene glycol dimethacrylate sharply decreases at the pH where volume phase transition occurs. The polymer microgels cross-linked with 40 and 45 mol% of diethylene glycol dimethacrylate caused about 50% T 2 reduction with decreasing pH from 6.8 to 6.4. These results demonstrated that responses of microgels to a range of neutral pH can be easily tuned by using appropriate cross-linkers with certain cross-linking degree. This approach can be useful in developing highly sensitive molecular sensors for magnetic resonance imaging (MRI) of tissue pH values.

The solubility values and thermodynamic parameters of a natural phytomedicine/nutrient piperine (PPN) in Transcutol-HP (THP) + water combinations were determined. The mole fraction solubilities ( x e ) of PPN in THP + water combinations were recorded at T = 298.2-318.2 K and p = 0.1 MPa by the shake flask method. Hansen solubility parameters (HSPs) of PPN, pure THP, pure water and THP + water mixtures free of PPN were also computed. The x e values of PPN were correlated well with "Apelblat, Van't Hoff, Yalkowsky-Roseman, Jouyban-Acree and Jouyban-Acree-Van't Hoff" models with root mean square deviations of < 2.0%. The maximum and minimum x e value of PPN was found in pure THP (9.10 × 10 -2 at T = 318.2 K) and pure water (1.03 × 10 -5 at T = 298.2 K), respectively. In addition, HSP of PPN was observed more closed with that of pure THP. The thermodynamic parameters of PPN were obtained using the activity coefficient model. The results showed an endothermic dissolution of PPN at m = 0.6-1.0 in comparison to other THP + water combinations studied. In addition, PPN dissolution was recorded as entropy-driven at m = 0.8-1.0 compared with other THP + water mixtures evaluated.

The purpose of this study was to investigate the permeation of the glycol ethers, 2-ethoxyethanol (2-EE) and 2-butoxyethanol (2-BE) through disposable, nitrile exam gloves using a modified American Society for Testing and Materials (ASTM) closed-loop module. The purple unsupported, unlined, powderless nitrile glove from Kimberly-Clark was challenged by the two pure glycol ethers. Their permeation parameters were measured with the aid of a 2.54 cm ASTM F739 closed-loop permeation cell using water collection at 35.0 ± 0.5°C in a moving tray water bath, and capillary gas chromatography-mass spectrometry for quantification. Each set of experiments consisted of four standard permeation cells with water as the collection solvent. The steady state permeation rate for 2-EE of 4.83 ± 0.45 µg/cm 2 /min was about 4 times that of 2-BE (1.27 ± 0.11 µg/cm 2 /min). Permeation of the more nonpolar 2-BE was less than for 2-EE. Both solvents exceeded the ASTM threshold normalized breakthrough time in the closed-loop testing module. Glove samples failed to pass permeation criteria defined by Kimberly Clark and Ansell. Such gloves are not recommended as personal protective equipment for exposure to 2-butoxyethanol or 2-ethoxyethanol, even for very short period exposures. Glove manufacturers should reconsider existing permeation testing method for low volatile compounds and apply the closed-loop module due to higher sensitivity and accuracy.

The solubility profile of codeine phosphate in the carbitol and 2-propanol mixtures at 293.2-313.2 K are determined and correlated with some developed cosolvency models. Moreover, the density values of codeine phosphate saturated solutions are also determined and fitted with the Jouyban-Acree model. The model accuracy is investigated by calculating the mean relative deviations (MRDs%). The thermodynamic parameters of codeine phosphate dissolution in the non-aqueous mixtures of carbitol and 2-propanol are also computed by using van't Hoff and Gibbs equations.

Digital inkjet printing has been widely used in textile industry. The quality of dye solutions and ink-jet droplets limits the ink-jet printing performance, which is very important for obtaining high-quality ink-jet printing images on fabrics. In this paper, we introduced diethylene glycol (DEG) into the dye solutions of Reactive Blue 49 and Reactive Orange 13, respectively, and investigated the interaction between dye chromophores and DEG molecules. Results indicated that the dye chromophores were featured in the aggregation. Adding DEG into the dye solution could effectively disaggregate clusters of reactive dyes, and eliminate satellite ink droplets, thus improving the resolution of the ink-jet printing image on fabrics. Under the same DEG concentration, the disaggregation effect was more obvious in Orange 13 than in Reactive Blue 49. Higher DEG concentration was required in Reactive Orange 13 solution for creating complete and stable ink drops. The surface tension and viscosity of the dye solutions were measured, and printing performance on cotton fabrics was evaluated. The interaction mechanism between dye chromophores and DEG molecules was also investigated. Results from this work are useful for high-quality ink-jet printing images on fabrics.

Multilayer materials used in food packaging are commonly manufactured with a polyurethane adhesive layer in its structure that may contain cyclic esters oligomers as potential migrants. However, little is known about their toxicity. In this work, two cyclic esters of polyurethane are evaluated in migration from 20 multilayer packaging samples. They were composed by adipic acid (AA), diethylene glycol (DEG) and isophthalic acid (IPA) and their structure was AA-DEG and AA-DEG-IPA-DEG. The concentration of these compounds in migration exceeded the maximum level established by Regulation EU/10/2011 (10 ng g -1 ). Bioaccessibility of both compounds was evaluated by studying gastric and intestinal digestion. The studies showed that the concentration of the compounds decreased during digestion and that their hydrolysed molecules increased. Furthermore, endocrine activity in vitro assays were performed. A weak androgen receptor antagonism was identified, whereas no arylhydrocarbon receptor activity or binding to the thyroid hormone transport protein was found., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Poly(methacrylate oligoethylene glycol dendron-co-citric acid) (PGCA) that is based on citric acid and oligoethylene glycol (OEG) dendrons is utilized as a nanomaterial for the removal of heavy metal ions from aqueous solution. PGCA shows excellent solubility in aqueous solution and realizes satisfactory removal efficacy for Pb 2+ ions; the removal rate exceeds 95 %. In addition, PGCA can be utilized in Chinese herbal decoctions; the removal rate of Pb 2+ ions in the ligusticum wallichii decoction exceeds 90 %, meanwhile the concentration of the active ingredient, namely, ferulic acid, is maintained. In this nanoadsorbent, citric acid provides the active site for the chelation of heavy metal ions, and OEG dendron serves as a protective layer that reduces the opportunity for carboxyl groups to be occupied by other ingredients. In summary, nanomaterial PGCA is designed and synthesized successfully that can be applied as a nanoadsorbent for the removal of Pb 2+ ions from aqueous solution, especially in Chinese herbal decoctions that have acidic compounds as active ingredients., Competing Interests: Declaration of Competing Interest No conflict of interest exists in the submission of this manuscript, and manuscript is approved by all authors for publication., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Anthrone is a routinely used reagent for estimating carbohydrates (Polysaccharides) in research, development and pharmaceutical applications. In presence of sulphuric acid, the polysaccharide gets hydrolyzed to monosaccharides in the form of hydroxymethyl furfural or furfural. The furfural then reacts with anthrone to form a green color complex with a maximum absorbance at 625 nm. Though anthrone reacts well with polysaccharides containing hexoses (such as glucose and galactose) and rhamnose, it is less reactive with uronic acids (such as glucuronic acid and galacturonic acid) and hexosamines (such as fucosamine, glucosamine, galactosamine, mannosamine, pneumosamine). Here, we report a novel reagent, 2-Phenoxyethanol, which reacts with furfural or hydroxymethyl furfural resulting in higher absorptivity. This method is rapid, sensitive, simple and direct, and can be used for quantitative determination of any type of carbohydrate that contains neutral sugars and uronic acids. For these saccharides, the sensitivity of the assay using 2-Phenoxyethanol (2-PE) is twice over anthrone method. Uronic acids show improved sensitivity using 2-PE over Phenol and it is more than twice with glucuronic acid. 2-PE reagent method has greater application for quantification of carbohydrates when present in low concentration in vaccines/biologicals., (Copyright © 2020 Elsevier Inc. All rights reserved.)

meta -Tetra(hydroxyphenyl)chlorin (mTHPC) is one of the most potent second-generation photosensitizers, clinically used for photodynamic therapy (PDT) of head and neck squamous cell carcinomas. However, improvements are still required concerning its present formulation (i.e., Foscan, a solution of mTHPC in ethanol/propylene glycol (40:60 w/w)), as mTHPC has the tendency to aggregate in aqueous media, e.g., biological fluids, and it has limited tumor specificity. In the present study, polymeric micelles with three different diameters (17, 24, and 45 nm) based on benzyl-poly(ε-caprolactone)- b -poly(ethylene glycol) (PCL n -PEG; n = 9, 15, or 23) were prepared with mTHPC loadings ranging from 0.5 to 10 wt % using a film-hydration method as advanced nanoformulations for this photosensitizer. To favor the uptake of the micelles by cancer cells that overexpress the epidermal growth factor receptor (EGFR), the micelles were decorated with an EGFR-targeted nanobody (named EGa1) through maleimide-thiol chemistry. The enhanced binding of the EGFR-targeted micelles at 4 °C to EGFR-overexpressing A431 cells, compared to low-EGFR-expressing HeLa cells, confirmed the specificity of the micelles. In addition, an enhanced uptake of mTHPC-loaded micelles by A431 cells was observed when these were decorated with the EGa1 nanobody, compared to nontargeted micelles. Both binding and uptake of targeted micelles were blocked by an excess of free EGa1 nanobody, demonstrating that these processes occur through EGFR. In line with this, mTHPC loaded in EGa1-conjugated PCL 23 -PEG (EGa1-P 23 ) micelles demonstrated 4 times higher photocytotoxicity on A431 cells, compared to micelles lacking the nanobody. Importantly, EGa1-P 23 micelles also showed selective PDT against A431 cells compared to the low-EGFR-expressing HeLa cells. Finally, an in vivo pharmacokinetic study shows that after intravenous injection, mTHPC incorporated in the P 23 micelles displayed prolonged blood circulation kinetics, compared to free mTHPC, independently of the presence of EGa1. Thus, these results make these micelles a promising nanomedicine formulation for selective therapy.

Giardiasis, one of the most common causes of diarrhoeal disease, is caused by gastrointestinal protozoal parasites of the genus Giardia. Metronidazole is the most commonly used drug to treat giardiasis. However, metronidazole resistance is increasingly common, making the development of new anti-giardial drugs a high priority. A panel of 11 compounds previously identified in T. ferdinandiana fruit extracts were investigated for the ability to inhibit G. duodenalis proliferation. Eight of the 11 compounds inhibited the growth of all three G. duodenalis strains. 2,3-Dihydroxyphenyl B-D-glucopyranosiduronic acid (DPGA) was the most potent anti-giardial compound, with IC 50 values as low as 126 μM (38 μg/mL). Notably, DPGA inhibited a metronidazole-resistant G. duodenalis strain with similar activity as determined for the metronidazole-sensitive strains. Furthermore, the activity of DPGA was greatly potentiated when it was tested in combination with ascorbic acid, to approximately 17 μM (5 μg/mL) for the metronidazole-sensitive G. duodenalis strains and 40 μM (12 mg/mL) for the resistant strain. The T. ferdinandiana tannins (gallic acid and chebulic acid) were moderate inhibitors of G. duodenalis growth when tested in combination with ascorbic acid, although they had only low levels of activity when tested alone. All of the tested compounds (and their combinations with ascorbic acid) displayed low toxic effects and all compounds are conformed to Lipinski's rules of 5 with few violations, indicating their potential as drug leads and chemotherapies for the treatment and prevention of giardiasis.

Bone is a randomized, complex porous network which researchers have tried to mimic within bone tissue engineering scaffolds. The objective of this study was to understand the effects of random and controlled scaffold porosity on the release kinetics of vitamin D 3 to determine if a designed porous structure was comparable in effectiveness on osteoblast proliferation to the randomized essence of natural bone. In this study, porous tricalcium phosphate (TCP) scaffolds were prepared by fugitive material removal method using naphthalene and 3D printing to model random and controlled porosity, respectively. Scaffold comparison was made based on open pore volume percentage of which naphthalene scaffolds had 45.8 ± 1.5% and 3D printed scaffolds had 48.9 ± 2.5%, Comparative analysis of traditional bioceramic processing to additive manufacturing is limited especially regarding drug release kinetics. Results showed the naphthalene scaffold surface area was only 0.3% that of 3D printed scaffolds due to the lower open pore interconnectivity. This increase in surface area produced higher release of drug and osteoblast proliferation in 3D printed scaffolds comparatively. By 11 days, osteoblast proliferation was enhanced by 64% from scaffolds manufactured using 3D printing compared to traditional processing. Understanding the effects of processing methods of TCP scaffolds on the release kinetics of vitamin D 3 and the system effects on cells can aid in low load bearing applications for bone tissue engineering.

The synthesis of a photoresponsive amphiphilic diblock quarterpolymer containing 5-vinyl-1-naphthol (VN) as a photostable photoacidic comonomer is presented. The preparation is realized via a sequential reversible addition fragmentation chain transfer (RAFT) polymerization starting from a nona(ethylene glycol) methyl ether methacrylate (MEO 9 MA/"O") hydrophilic block, which is then used as a macro-RAFT agent in the terpolymerization of styrene (S), 2-vinylpyridine (2VP), and TBS-protected VN (tVN). The terpolymerization proceeds in a controlled fashion and two diblock quarterpolymers, P(O m )-b-P(S x -co-2VP y -co-VN z ), with varying functional comonomer compositions are prepared. These diblock quarterpolymers form spherical core-corona micelles in aqueous media according to dynamic light scattering (DLS) and cryogenic transmission electron microscopy (cryo-TEM). Upon irradiation, the photoacids within the micellar core experience a drastic increase in acidity causing a proton transfer from the photoacid to neighboring 2VP units. As a result, the hydrophilic/hydrophobic balance of the entire assembly is shifted, and the encapsulated cargo is released., (© 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Amyvid (florbetapir f18, [ 18 F]AV-45, [ 18 F]5) was the first FDA-approved positron emission tomography imaging agent targeting β-amyloid (Aβ) plaques for assisting the diagnosis of Alzheimer disease. This work aimed to improve the [ 18 F]AV-45 ([ 18 F]5) preparation by using solid-phase extraction (SPE) purification. [ 18 F]AV-45 ([ 18 F]5) was synthesized by direct nucleophilic radiofluorination of O-tosylated precursor (1 mg) at 120°C in anhydrous dimethyl sulfoxide (DMSO), followed by acid hydrolysis of the N-Boc protecting group. Purification was accomplished by loading the crude reaction mixture to a cartridge (Oasis HLB 3 cc) and eluting with different combinations of solvents. This method removed the chemical impurity while leaving [ 18 F]AV-45 ([ 18 F]5) on the cartridge. The final dose was eluted by ethanol. [ 18 F]AV-45 ([ 18 F]5) was produced within 51 minutes (radiochemical yield 42.7 ± 5.9%, decay corrected, n = 3), and the radiochemical purity was greater than 95%. Total chemical impurity per batch (24.1 ± 2.7 μg per batch) was below the limit described in the package insert of Amyvid, florbetapir f18 (chemical mass: less than 50 μg/dose). In summary, [ 18 F]AV-45 ([ 18 F]5) was produced efficiently and reproducibly using a cartridge-based SPE purification. This method brings the process closer for routine preparation, similar to the commercially used [ 18 F]FDG., (© 2019 John Wiley & Sons, Ltd.)

The asymmetric resolution of racemic 1-phenyl-1,2-ethanediol (PED) to (S)-PED by Kurthia gibsonii SC0312 (K. gibsonii SC0312) was conducted in a biphasic system comprised of an organic solvent and aqueous phosphate buffer. The impacts of organic solvents on the whole cell catalytic activity, metabolic activity, membrane integrity, and material distribution were first evaluated. The results showed that all organic solvents, except for dibutyl phthalate, showed a detrimental effect on the metabolic activity of the cells, especially for those with low log P values. All organic solvents were capable of changing the membrane permeability and membrane integrity of the cells. Moreover, some organic solvents showed a good extraction of the oxidation product. Finally, a high yield of 47.7 % of (S)-PED was obtained by the asymmetric resolution of racemic PED using K. gibsonii SC0312 in a biphasic system under the optimal conditions: racemic PED 120 mM, temperature 35 °C, reaction time 6 h, 180 rpm, and a volume ratio of dibutyl phthalate to aqueous phosphate buffer of 1:1. The optical purity of (S)-PED increased from 51.3 % to >99 %. This work described an efficient approach to improve reaction efficiency, and constructed a highly effective biphasic reaction system for the fabrication of (S)-PED via K. gibsonii SC0312., (Copyright © 2019 Elsevier B.V. All rights reserved.)

HL235 is a new cathepsin K inhibitor designed and synthesized to treat osteoporosis. Since HL235 has poor aqueous solubility, a self-microemulsifying drug delivery system (SMEDDS) was formulated to enhance its oral bioavailability. A solubility study of HL235 was performed to select a suitable oil, surfactant and cosurfactant. Pseudoternary phase diagrams were plotted to identify the microemulsion region and to determine the range of components in the isotropic mixture. D-optimal mixture design and a desirability function were introduced to optimize the SMEDDS formulation for the desired physicochemical characteristics, i.e., high drug concentration at 15 min after dilution with simulated gastric fluid (SGF) and high solubilization capacity. The optimized HL235-loaded SMEDDS formulation consisted of 5.0% Capmul MCM EP (oil), 75.0% Tween 20 (surfactant) and 20.0% Carbitol (cosurfactant). The droplet size of the microemulsion formed by the optimized formulation was 10.7 ± 1.6 nm, and the droplets were spherical in shape. Pharmacokinetic studies in rats showed that the relative oral bioavailability of the SMEDDS formulation increased up to 3.22-fold compared to its solution in DMSO:PEG400 (8:92, v/v). Thus, the formulation of SMEDDS optimized by D-optimal mixture design could be a promising approach to improve the oral bioavailability of HL235., (Copyright © 2019. Published by Elsevier B.V.)

Objective: The aim of the present study was to design nanocarriers for the topical application of rivastigmine., Methods: The effect of cosurfactants, hydrophilic gel and loading amount on the permeability of rivastigmine through rat skin was evaluated. Skin irritation tests and stability tests were performed to evaluate the utility of tested formulations., Results: The results showed that the microemulsion formation and characteristics of drug-loaded formulations were related to many parameters of the components. When using microemulsion systems as a vehicle, the permeation rate remarkably increased about 13.2~24.3-fold and the lag time was significantly shortened from 24 h to 4.7 h. Formulations containing a cosurfactant of Diethylene Glycol Monobutyl Ether (DEGBE) showed higher enhancement effect, while increasing the loading dose from 0.5% to 5% further increased the flux about 2.1-fold and shortened the lag time., Conclusion: The drug-loaded experimental formulation did not cause skin irritation and had good stability at 20ºC and 40ºC storage for at least 3 months. The result showed that gel-based microemulsion formulation could be a promising approach for topical administration., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A lipase-triggered drug release nanoplatform (PGL-DPP-FLU NPs) for multi-modal antifungal therapy is developed. The lipases secreted by C. albicans can accelerate FLU release. The ROS and heat produced by PGL-DPP-FLU NPs make C. albicans more vulnerable to FLU, thereby PGL-DPP-FLU NPs exhibit high performance for combating azole-resistant C. albicans biofilms and wound infection.

Poly(glycidyl methacrylate)-co-(ethylene dimethacrylate) [poly(GMA-co-EDMA)] monoliths were used as a support to grow a zeolitic imidazolate framework-8 (ZIF-8) via layer-by-layer self-assembly. Pepsin, acting as as chiral selector, was covalently linked to the surface of the amino-modified ZIF-8 through the Schiff base method. The material was characterized by scanning electron microscopy, thermogravimetric analysis, X-ray diffraction, Fourier transform infrared spectroscopy and elemental analysis. The pepsin-ZIF-8-poly(GMA-co-EDMA) column was utilized to the enantioseparation of the racemic forms of hydroxychloroquine (HCQ), chloroquine (CHQ), hydroxyzine (HXY), nefopam (NEF), clenbuterol (CLE) and amlodipine (AML). In comparison with a pepsin-poly(GMA-co-EDMA) monolithic column (without self-assembled ZIF-8 nanoparticles), the resolution is strongly enhanced (HCQ: 0.34 → 2.50; CHQ: 0.45 → 1.97; HXY: 0.39 → 1.43; NEF: 0.27 → 0.81; CLE: 0 → 0.81; AML: 0.16 → 0.72). Effects of self-assembly layers of ZIF-8, pepsin concentration, buffer pH values and applied voltage were investigated with hydroxychloroquine as the model analyte. The reproducibility of run-to-run, day-to-day and column-to-column were explored, and found to be satisfactory. Graphical abstractSchematic representation of capillary electrochromatography (CEC) systems with a pepsin-zeolitic imidazolate framework-8 (ZIF-8) modified poly(glycidyl methacrylate)-co-(ethylene dimethacrylate) [poly(GMA-co-EDMA)] monolithic column as stationary phases for separation of basic racemic drugs. ZIF-8 modified column was prepared via layer-by-layer self-assembly.

Purpose: Directing nanoparticles to cancer cells without using antibodies is of great interest. Subtle changes to the surface chemistry of nanoparticles can significantly affect their biological fate, including their propensity to associate with different cell populations. For instance, nanoparticles functionalized with thiol-reactive groups can potentially enhance association with cells that over-express cell-surface thiol groups. The potential of such an approach for enhancing drug delivery for childhood acute lymphoblastic leukemia (ALL) cells has not been investigated. Herein, we investigate the impact of thiol-reactive star polymers on the cellular association and the mechanisms of uptake of the nanoparticles., Methods: We prepared fluorescently labeled star polymers functionalized with an mPEG brush corona and pyridyl disulfide to examine how reactivity to exofacial thiols impacts cellular association with ALL cells. We also studied how variations to the mPEG brush composition could potentially be used as a secondary method for controlling the extent of cell association. Specifically, we examined how the inclusion of shorter diethylene glycol brush moieties into the nanoparticle corona could be used to further influence cell association., Results: Star polymers incorporating both thiol-reactive and diethylene glycol brush moieties exhibited the highest cellular association, followed by those functionalized solely with thiol reactive groups compared to control nanoparticles in T and B pediatric ALL patient-derived xenografts harvested from the spleens and bone marrow of immunodeficient mice. Transfection of cells with an early endosomal marker and imaging with correlative light and electron microscopy confirmed cellular uptake. Endocytosis inhibitors revealed dynamin-dependent clathrin-mediated endocytosis as the main uptake pathway for all the star polymers., Conclusion: Thiol-reactive star polymers having an mPEG brush corona that includes a proportion of diethylene glycol brush moieties represent a potential strategy for improved leukemia cell delivery., Competing Interests: The authors have no conflicts of interest or financial disclosures to declare., (© 2019 Bayat et al.)

In the present study, a novel transdermal delivery system was developed and its advantages were demonstrated. Ibuprofen is a commonly used anti-inflammatory, antipyretic, and analgesic drug; however, because of its short biological half-life, it must be frequently administered orally and is highly irritating to the digestive tract. To prepare a novel transdermal delivery system for ibuprofen, a microemulsion was used as a drug carrier and dispersed in a hyaluronic acid-based hydrogel (ME/Gel) to increase percutaneous drug absorption while avoiding gastrointestinal tract irritation. The prepared microemulsion had a droplet size of ~ 90 nm, and the microemulsion had good stability in the hydrogel. Rheological tests revealed that the ME/Gel is a pseudoplastic fluid with decreased viscosity and increased shear rate. It displayed a certain viscoelasticity, and the microemulsion distribution displayed minor effects on the rheological characteristics of the hydrogel system. There was no significant difference in the rheology of the ME/Gel at 25°C and 32°C (normal skin surface temperature), which is beneficial for clinical application. Drug transdermal flux was significantly higher than that of the hydrogel and commercial cream groups (p < 0.01). The 24-h cumulative drug permeation amount was 1.42-fold and 2.52-fold higher than that of the hydrogel and cream groups, respectively. By loading into the ME/Gel, the cytotoxicity of the drug to HaCaT cells was reduced. These results indicate that the prepared ME/Gel can effectively improve transdermal ibuprofen delivery and the biosafety of the drug and could therefore have applicability as a drug delivery system.

The objective of present study was to develop and evaluate lipid vesicular transdermal system of iloperidone. Liposomes were prepared successfully using thin film hydration method. With aim of enhancing permeation, cholesterol from liposomes was replaced with transcutol to give PEVs. Liposomes and PEVs were evaluated for particle size, shape, entrapment efficiency, viscosity and release study. The vesicles were incorporated in 0.5% of Carbopol gel and evaluated. Particle size of liposomes and PEVs was found between 200-300 nm and entrapment efficiency was found 80-90%w/w. The transdermal gels were homogeneous, spreadable having acceptable pH and drug content between 90-100%.In ex vivo studies, both liposomes and PEVs showed relatively higher skin deposition and permeation of Iloperidone than the plain drug without vesicles. The in vivo pharmacokinetics studies showed relative bioavailability of the PEV loaded gel as 62% and 166% when compared to the oral drug and gel without vesicles respectively. Pharmacodynamic studies showed FRT and HRT delay responses of the transdermal gel systems were significant[p < 0.05] as compared to control at the end of 24 hs. Thus, it can be concluded that transdermal delivery system can be a promising approach for sustained delivery of Iloperidone., (Copyright © 2019 Elsevier B.V. All rights reserved.)

An alternative CE-(indirect ultraviolet) method for the analysis of inorganic and organic anions in ethylene glycol-based engine coolants is presented using a BGE with 4 mM pyromellitic acid and 3.4 mM 1,6-hexamethylene diamine, pH 3. Baseline separation of six inorganic (e.g. nitrite, nitrate, and sulfate) and five organic anions (e.g. acetic and glycolic acid) was achieved. Quantification of 8 out of 11 specified anions was possible in stressed engine coolant samples after simple aqueous dilution. LODs between 0.8 and 15.1 mg/L with RSD values of peak areas between 2.6 and 11.9% were obtained. Some limitations due to matrix effects can be overcome with slight adaptations of the BGE. The flexibility of the method is vital regarding the increasing demands for the composition of engine coolants for pollution reduction., (© 2019 The Authors. Electrophoresis published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Populations of cells exhibit variations in biochemical activity, resulting from many factors including random stochastic variability in protein production, metabolic and cell-cycle states, regulatory mechanisms, and external signaling. The development of methods for the analysis of single cells has allowed for the measurement and understanding of this inherent heterogeneity, yet methods for measuring protein activities on the single-cell scale lag behind their genetic analysis counterparts and typically report on expression rather than activity. This paper presents an approach to measure protein tyrosine phosphatase (PTP) activity in individual cells using self-assembled monolayers for matrix-assisted laser desorption/ionization mass spectrometry. Using flow cytometry, individual cells are first sorted into a well plate containing lysis buffer and a phosphopeptide substrate. After lysis and incubation-during which the PTP enzymes act on the peptide substrate-the reaction substrate and product are immobilized onto arrays of self-assembled monolayers, which are then analyzed using mass spectrometry. PTP activities from thousands of individual cells were measured and their distributions analyzed. This work demonstrates a general method for measuring enzyme activities in lysates derived from individual cells and will contribute to the understanding of cellular heterogeneity in a variety of contexts.

Trial-and-error approach to formulation development is long and costly. With growing time and cost pressures in the pharmaceutical industry, the need for computer-based formulation design is greater than ever. In this project, emulgels were designed and optimized using Formulating for Efficacy™ (FFE) for the topical delivery of ibuprofen. FFE helped select penetration enhancers, design and optimize emulgels and simulate skin penetration studies. pH, viscosity, spreadability, droplet size and stability of emulgels were evaluated. Franz cell studies were performed to test in vitro drug release on regenerated cellulose membrane, drug permeation in vitro on Strat-M® membrane and ex vivo on porcine ear skin, a marketed ibuprofen gel served as control. Emulgels had skin compatible pH, viscosity and spreadability comparable to a marketed emulgel, were opaque and stable at 25 °C for 6 months. Oleyl alcohol (OA), combined with either dimethyl isosorbide (DMI) or diethylene glycol monoethyl ether (DGME) provided the highest permeation in 24 h in vitro, which was significantly higher than the marketed product (p < 0.01). OA + DGME significantly outperformed OA ex vivo (p < 0.05). The computer predictions, in vitro and ex vivo penetration results correlated well. FFE was a fast, valuable and reliable tool for aiding in topical product design for ibuprofen., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In this study, we report a novel pH and temperature responsive paclitaxel-loaded drug delivery system based on chitosan and di(ethylene glycol) methyl ether methacrylate. This was functionalized with hyaluronic acid to permit active targeting of CD44-overexpressing human breast cancer cells. The resultant HA-CS-g-PDEGMA-PTX nanoparticles (NPs) have small and uniform sizes (˜170 nm), a high drug loading (13.6 ± 1.3%) and high encapsulation efficiency (76.2 ± 8.5%). Cell viability and confocal microscopy experiments demonstrated that the NPs could effectively target and kill MDA-MB-231 human breast cancer cells, but were much less toxic to healthy human umbilical vein endothelial cells. In vivo biodistribution studies in mice showed that the NPs accumulated in the tumor site, while free drug was distributed more widely and rapidly cleared from the body. Histopathological studies revealed that the NPs led to enhanced apoptosis in the tumor site, which resulted in reduced tumor growth. The NPs prepared in this work have great potential for the treatment of breast cancers, and further offer a platform with which to target other cancers., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Activators regenerated by electron transfer atom transfer radical polymerization (AGET ATRP) were firstly used in suspension polymerization to prepare macroporous microspheres based on a copolymer of glycidyl methacrylate and ethylene glycol dimethacrylate. Compared to conventional radical polymerization (CRP), the microspheres by AGET ATRP showed more homogeneous structure, larger pores, and higher protein binding capacity. The body of microspheres are formed by the large clusters resulted from the aggregated little particles. The size of the particles in microspheres by AGET ATRP was 10-300 nm which was smaller than that (400-800 nm) of the microspheres by CRP. AGET ATRP gave larger pore size (275 ± 5 nm) and surface area (59.3 ± 1 m 2 /g) than CRP (234 ± 5 nm, 37.5 ± 1 m 2 /g). The microspheres were modified with polyethylene imine for anion resins that were evaluated in term of its protein binding capacity. The results indicated that the static (69 ± 0.5 mg/mL) and dynamic binding capacity (61 ± 0.5 mg/mL) of proteins on modified microspheres by AGET ATRP were higher than that (34 ± 0.5 mg/mL and 19 ± 0.5 mg/mL) by CRP. Meanwhile, the proteins binding capacity on the microspheres by AGET ATRP decreased only less than 10% when the flow rate increased 10 times. These macroporous media show a large potential in rapid separation of proteins., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Botanical triterpene celastrol is a candidate drug for the treatment of obesity, except for concerns over the safety in clinical application. The present study was designed to investigate the anti-obesity, anti-inflammatory and toxic activities of celastrol-loaded nanomicelles (nano-celastrol) in diet-induced obese mice. Celastrol was loaded into PEG-PCL nanoparticles, yielding nano-celastrol with optimal size, spherical morphology, good bioavailability, slower peak time and clearance in mice. Nano-celastrol (5 or 7.5 mg/kg/d of celastrol) was administered into diet-induced obese C57BL/6 N male mice for 3 weeks. As result, higher dose nano-celastrol reduced body weight and body fat mass in an equally effective manner as regular celastrol, although lower dose nano-celastrol showed less activity. Similarly, nano-celastrol improved glucose tolerance in mice equally well as regular celastrol, whereas higher dose nano-celastrol improved the response to insulin. As for macrophage M1/M2 polarization in liver, nano-celastrol reduced the expression of macrophage M1 biomarkers (e.g., IL-6, IL-1β, TNF-α, iNOS) in a dose-dependent manner and marginally increased the expression of macrophage M2 biomarkers (e.g., Arg-1, IL-10). Moreover, celastrol could cause anus irritation and disturb intestinal and colonic integrity, whereas nano-celastrol did not cause any injury to mice. Collectively, nano-celastrol represents a translatable therapeutic opportunity for treating diet-induced obesity in humans., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Organic-inorganic oligo(ethylene glycol)-polyhedral oligomeric silsesquioxanes (OEG n -POSS) hybrid materials are woven into macroscopically shaped entities by thiol-ene chemistry. The mechanical behavior and interfacial nature of the OEG n -POSS materials are easily tailored by changing the length of OEG n . The nanostructured OEG n -POSS materials exhibited excellent bioactivity to form hydroxyapatite, whose morphology was also dependent on the molecular weight of OEG n . Among them, OEG 2 -POSS materials enhanced the in vitro differentiation of adipose-derived stem cells to osteoblasts and promoted the in vivo bone formation within a femoral condyle defect site, but they could be limited by the mismatch rates between the degradation and new bone formation. Thus, OEG 2 -POSS could be practically applied for bone regeneration by optimizing the degradation rate based on its key structural features, which would be of great benefit to bone tissue engineering in the future.