Development of a method for quantitative determination of the cytotoxic agent piplartine (piperlongumine) in multiple skin layers

This study reports the development of a simple and reproducible method, with high rates of recovery, to extract the cytotoxic agent piplartine from skin layers, and a sensitive and rapid UV‐HPLC method for its quantification. Considering the potential of piplartine for topical treatment of skin cancer, this method may find application for formulation development and pharmacokinetics studies to assess cutaneous bioavailability. Porcine skin was employed as a model for human tissue. Piplartine was extracted from the stratum corneum (SC) and remaining viable skin layers (VS) using methanol, vortex homogenization and bath sonication, and subsequently assayed by HPLC using a C₁₈ column, and 1:1 (v/v) acetonitrile–water (adjusted to pH 4.0 with acetic acid 0.1%) as mobile phase. The quantification limit of piplartine was 0.2 μg/mL (0.6 μm ), and the assay was linear up to 5 μg/mL (15.8 μm ), with within‐day and between‐days assay coefficients of variation and relative errors <15%. Piplartine recovery from SC and VS varied from 86 to 96%. The method was suitable to assay samples from skin penetration studies, enabling detection of differences in cutaneous delivery in different skin compartments resulting from treatment with various formulations and time periods.     

DLSFEM–PML formulation for the steady-state response of a taut string on visco-elastic support under moving load

Meccanica - The numerical solution of the steady-state response of a uniform taut string on visco-elastic support under a concentrated transverse moving load is addressed. By recasting the...     

Development and validation of a bioanalytical method by LC‐MS/MS for the quantification of the LAFIS 10 – an antimalarial candidate – and its pharmacokinetics first evaluation

A rapid and highly sensitive method by LC‐MS/MS was developed and validated for the quantification of an antimalarial candidate (LAFIS10) in rat plasma using dexamethasone as internal standard (IS). The chromatographic separation was performed with a Poroshell 120 EC‐C₁₈ column. The mobile phase consisted of water (A) and acetonitrile (B), both containing 10 m m of ammonium formate and 0.1% formic acid, delivered in the form of elution gradient. The LAFIS10 was monitored using an electrospray ionization interface operating in the positive mode in multiple reaction monitoring mode, monitoring the transitions 681.47 → 538.2 for LAFIS10 and 393.20 → 355.30 for the IS. The flow rate was 500 μL/min. The column temperature was kept at 40 °C and the injection volume was 2 μL. The lower limit of quantification was of 10 ng/mL and linearity between 10 and 1000 ng/mL was observed, with an R² > 0.99. The accuracy of the method was >90%. The relative standard deviations intra‐ and interday were <8.80 and <6.37%, respectively. The method showed sensitivity, linearity, precision, accuracy and selectivity required to quantify LAFIS 10 in preclinical pharmacokinetic studies according to criteria established by the US Food and Drug Administration and European Medicines Agency. Copyright © 2014 John Wiley & Sons, Ltd.     

Green solvent approach for printable large deformation thermoplastic elastomer based piezoresistive sensors and their suitability for biomedical applications

Composites based on biocompatible thermoplastic elastomer styrene‐ethylene/butylene‐styrene (SEBS) as matrix and multi‐walled carbon nanotubes (MWCNT) as nanofillers show excellent mechanical and piezoresistive properties from low to large deformations. The MWCNT/SEBS composites have been prepared following a green solvent approach, to extend their range of applicability to biomedical applications. The obtained composites with 2, 4, and 5 wt % MWCNT content provide suitable piezoresistive response up to 80% deformation with a piezoresistive sensibility near 2.7, depending on the applied strain and MWCNT content. Composite sensors were also developed by spray and screen printing and integrated with an electronic data acquisition system with RF communication. The possibility to accurately control the composites properties and performance by varying MWCNT content, viscosity, and mechanical properties of the polymer matrix, shows the large potential of the system for the development of large deformation printable piezoresistive sensors. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016 , 54, 2092–2103     

Experimental Design in Nonlinear Case Applied to Hydrocracking Model: How Many Points Do We Need and Which Ones?

In this work, different experimental design techniques were applied to a hydrocracking conversion model (single response). The selection of points was carried out using Federov's algorithm from an experimental database containing 48 points. The sequential design methodology was also applied. Results show that the D‐optimality criterion can provide valuable information for determination of the minimum number of experiments required to achieve acceptable precision. It is shown that only 22 points are enough to estimate parameters instead of the original database of 48 points. If sequential techniques are used, only 13 points are needed. This work provides useful theoretical and practical guidelines for experimental design in single‐response problems.     

The powder X-band electron paramagnetic resonance spectroscopy of septet pyridyl-2,4,6-trinitrene

The first X-band EPR spectrum containing only non-overlapping signals of septet pyridyl-2,4,6-trinitrene and triplet pyridylnitrenes is reported. This spectrum was recorded after photolysis of 2,4,6-triazidopyridine in solid argon at 5 K. The zero-field splitting (ZFS) parameters of this trinitrene as well as of intermediate triplet mononitrenes and quintet dinitrenes formed at early stages of the photolysis were determined using the combination of modern computer line-shape spectral simulations and density functional theory (DFT) calculations. It was found that septet pyridyl-2,4,6-trinitrene has the record negative parameter D_S = −0.1031 cm⁻¹ among all known to date septet pyridyl-2,4,6-trinitrenes and may be of interest as a model multi-qubit spin system for investigations of quantum computation processing.     

Metal‐Free Synthesis of Functional 1‐Substituted‐1,2,3‐Triazoles from Ethenesulfonyl Fluoride and Organic Azides

The boom in growth of 1,4‐disubstituted triazole products, in particular, since the early 2000’s, can be largely attributed to the birth of click chemistry and the discovery of the Cu^I‐catalyzed azide–alkyne cycloaddition (CuAAC). Yet the synthesis of relatively simple, albeit important, 1‐substituted‐1,2,3‐triazoles has been surprisingly more challenging. Reported here is a straightforward and scalable click‐inspired protocol for the synthesis of 1‐substituted‐1,2,3‐triazoles from organic azides and the bench stable acetylene surrogate ethenesulfonyl fluoride (ESF). The new transformation tolerates a wide selection of substrates and proceeds smoothly under metal‐free conditions to give the products in excellent yield. Under controlled acidic conditions, the 1‐substituted‐1,2,3‐triazole products undergo a Michael addition reaction with a second equivalent of ESF to give the unprecedented 1‐substituted triazolium sulfonyl fluoride salts.