How to Obtain the Maximum Properties Flexibility of 3D Printed Ketoprofen Tablets Using Only One Drug-Loaded Filament?

The flexibility of dose and dosage forms makes 3D printing a very interesting tool for personalized medicine, with fused deposition modeling being the most promising and intensively developed method. In our research, we analyzed how various types of disintegrants and drug loading in poly(vinyl alcohol)-based filaments affect their mechanical properties and printability. We also assessed the effect of drug dosage and tablet spatial structure on the dissolution profiles. Given that the development of a method that allows the production of dosage forms with different properties from a single drug-loaded filament is desirable, we developed a method of printing ketoprofen tablets with different dose and dissolution profiles from a single feedstock filament. We optimized the filament preparation by hot-melt extrusion and characterized them. Then, we printed single, bi-, and tri-layer tablets varying with dose, infill density, internal structure, and composition. We analyzed the reproducibility of a spatial structure, phase, and degree of molecular order of ketoprofen in the tablets, and the dissolution profiles. We have printed tablets with immediate- and sustained-release characteristics using one drug-loaded filament, which demonstrates that a single filament can serve as a versatile source for the manufacturing of tablets exhibiting various release characteristics.     

Incorporation of β-Alanine in Cu(II) ATCUN Peptide Complexes Increases ROS Levels,DNA Cleavage and Antiproliferative Activity**

Redox-active Cu(II) complexes are able to form reactive oxygen species (ROS) in the presence of oxygen and reducing agents. Recently, Faller et al. reported that ROS generation by Cu(II) ATCUN complexes is not as high as assumed for decades. High complex stability results in silencing of the Cu(II)/Cu(I) redox cycle and therefore leads to low ROS generation. In this work, we demonstrate that an exchange of the α-amino acid Gly with the β-amino acid β-Ala at position 2 (Gly2→β-Ala2) of the ATCUN motif reinstates ROS production (^•OH and H₂O₂). Potentiometry, cyclic voltammetry, EPR spectroscopy and DFT simulations were utilized to explain the increased ROS generation of these β-Ala2-containing ATCUN complexes. We also observed enhanced oxidative cleavage activity towards plasmid DNA for β-Ala2 compared to the Gly2 complexes. Modifications with positively charged Lys residues increased the DNA affinity through electrostatic interactions as determined by UV/VIS, fluorescence, and CD spectroscopy, and consequently led to a further increase in nuclease activity. A similar trend was observed regarding the cytotoxic activity of the complexes against several human cancer cell lines where β-Ala2 peptide complexes had lower IC₅₀ values compared to Gly2. The higher cytotoxicity could be attributed to an increased cellular uptake as determined by ICP-MS measurements.     

In situ X‐ray data collection and structure phasing of protein crystals at Structural Biology Center 19‐ID

A prototype of a 96‐well plate scanner for in situ data collection has been developed at the Structural Biology Center (SBC) beamline 19‐ID, located at the Advanced Photon Source, USA. The applicability of this instrument for protein crystal diffraction screening and data collection at ambient temperature has been demonstrated. Several different protein crystals, including selenium‐labeled, were used for data collection and successful SAD phasing. Without the common procedure of crystal handling and subsequent cryo‐cooling for data collection at T = 100 K, crystals in a crystallization buffer show remarkably low mosaicity (<0.1°) until deterioration by radiation damage occurs. Data presented here show that cryo‐cooling can cause some unexpected structural changes. Based on the results of this study, the integration of the plate scanner into the 19‐ID end‐station with automated controls is being prepared. With improvement of hardware and software, in situ data collection will become available for the SBC user program including remote access.     

Nanosized carbon black as synergist in PP/POE-MA/IFR system for simultaneously improving thermal,electrical and mechanical properties

Nanosized carbon black (CB) was introduced into polypropylene/maleic anhydride-grafted polyolefin elastomer/intumescent flame retardant (PP/POE-MA/IFR) system to investigate the effect of nanofiller as synergist on thermal, electrical and mechanical properties of polymer composites. With 5 mass% CB into PP/POE-MA/IFR system (POFC5), the T_max (corresponded to the temperature at the maximum mass loss rate) under air was increased by 122.4 °C; its limited oxygen index was as high as 31.4%; its vertical burning rating (UL-94) reached V0, and the peak value of heat release rate was decreased to only 19% of neat PP in cone calorimeter testing. Moreover, PP composites exhibited good electrical conductivity with more than 1.6 mass% CB, which is a low loading level to reach the critical percolation concentration. In addition, a good balance on stiffness and toughness of PP composites was achieved; especially, Young’s moduli and impact strength of POFC5 were increased to 1.26 and 2.5 times in comparison with that of neat PP, respectively. These results indicated that CB was an effective synergist in multi-component PP composites to simultaneously improve thermal, electrical and mechanical properties.

     

Luminescence lifetime-based sensor for cyanide and related anions

A new Ru(II) complex is described which serves as a luminescence lifetime-based sensor for fluoride and cyanide anions (KF = 640 000 mol-1, KCN = 430 000 mol-1). This chromophore displays observable changes in its UV-vis and steady-state luminescence spectra upon cyanide binding. Prior to cyanide addition, this complex exhibits a single-exponential lifetime (tau = 377 +/- 20 ns). With increasing cyanide concentrations, the intensity decays are composed of two exponentials: long tau (320-370 ns) and short tau (13-17 ns). The average lifetimes shorten as a function of cyanide concentration since the fractional intensity shifts from an initial dominant long lifetime component to the short lifetime component. This work represents the first example of a direct method for the luminescence lifetime-based sensing of anions.     

Simple electrooptical sensors for inorganic anions

[reaction: see text] Electrooptical sensors consisting of a conjugated chromophore undergoing a change in color and a redox-active moiety such as quinone fused to the chromophore were synthesized. Strong changes in colorimetric and electrochemical properties were observed in the presence of inorganic anions. A unique anion-specific response was observed for fluoride, pyrophosphate, and acetate. DFT (B3LYP/6-31G) calculations performed for both "on/off" states of a sensor-fluoride model are in good agreement with the observed electrochemical and spectroscopic data.     

Evaluation of automated synthesis for chain and step‐growth polymerizations: Can robots replace the chemists?

This article explores current challenges in the use of automated parallel synthesizers in polymeric materials research. Four types of polymerizations were investigated: carbodiimide‐mediated polyesterification, diphenol phosgenation, free radical, and reversible addition‐fragmentation chain‐transfer (RAFT). Synthetic challenges of condensation polymerization, such as liquid and solid dispensing accuracy, dropwise addition, and toxic chemical handling, were successfully met using the automated synthesizer. Both solid and liquid dosing of the diphenol and diacid were successful for polyarylate synthesis. The high precision of liquid dispensing made it possible to achieve stoichiometric balance using reagent stock solutions. For all reactions, molecular weights and their reproducibility were comparable to those obtained with manual synthesis. For RAFT polymerizations, solvent and mol ratio of chain transfer reagent to initiator were successfully optimized on the automated synthesizer and a library of over 60 polymethacrylate copolymer compositions was generated. Considerable savings in time relative to manual methods were achieved when generating polymer libraries (e.g., 4.5× faster for 96 polymethacrylates and 20× faster for 45 for polycarbonates). © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 49–58, 2009     

A field deployable method for a rapid screening analysis of inorganic arsenic in seaweed

Inorganic arsenic (iAs) in 13 store-bought edible seaweed samples and 34 dried kelp (Laminaria digitata) samples was determined by a newly developed, field-deployable method (FDM) with the aid of a field test kit for arsenic in water. Results from the FDM were compared to results from speciation analysis achieved by using high performance liquid chromatography coupled to inductively coupled plasma mass spectrometry (HPLC-ICP-MS). The FDM consisted of a simple extraction method using diluted HNO₃ to quantitatively extract iAs without decomposing the organoarsenicals to iAs followed by the selective volatilisation of iAs as arsine (AsH₃) and subsequent chemo-trapping on a filter paper soaked in mercury bromide (HgBr₂) solution. Method optimization with a sub-set of samples showed 80–94% iAs recovery with the FDM with no matrix effect from organo-arsenic species in the form of dimethylarsinic acid (DMA) on the iAs concentration. The method displayed good reproducibility with an average error of ±19% and validation by HPLC-ICP-MS showed that the results from the FDM were comparable (slope = 1.03, R² = 0.70) to those from speciation analysis with no bias. The FDM can be conducted within an hour and the observed limit of quantification was around 0.05 mg kg^?1 (dry weight). This method is well suited for on-site monitoring of iAs in seaweed before it is harvested and can thus be recommended for use as a screening method for iAs in seaweed.

Open image in new window

Graphical abstract Screening seaweed for their inorganic arsenic concentration within one hour without bias has been made possible in the field by using a field deployable arsenic kit. Its accuracy and precision was compared to HPLC-ICPMS.