Role of Calixarene in Chemotherapy Delivery Strategies

Since cancer is a multifactorial disease with a high mortality rate, the study of new therapeutic strategies is one of the main objectives in modern research. Numerous chemotherapeutic agents, although widely used, have the disadvantage of being not very soluble in water or selective towards cancerous cells, with consequent side effects. Therefore, in recent years, a greater interest has emerged in innovative drug delivery systems (DDSs) such as calixarene, a third-generation supramolecular compound. Calixarene and its water-soluble derivatives show good biocompatibility and have low cytotoxicity. Thanks to their chemical–physical characteristics, calixarenes can be easily functionalized, and by itself can encapsulate host molecules forming nanostructures capable of releasing drugs in a controlled way. The encapsulation of anticancer drugs in a calixarene derivate improves their bioavailability and efficacy. Thus, the use of calixarenes as carriers of anticancer drugs could reduce their side effects and increase their affinity towards the target. This review summarizes the numerous research advances regarding the development of calixarene nanoparticles capable of encapsulating various anticancer drugs.     

Amperometric Sniffer for Volatile Amines Based on Paper‐Supported Room Temperature Ionic Liquids Enabling Rapid Assessment of Fish Spoilage

A gas sensors based on a room temperature ionic liquid (RTIL) supported on paper is proposed as amperometric sniffer for monitoring volatile amines (VAs) released from fish samples, in order to gain indication of their state of turning spoiled. It was used as a paper electrochemical detector (PED) for a flow injection system in which controlled headspace volumes in equilibrium with ice‐stored fish samples were directly injected. The performance of this RTIL‐PED sensor was preliminarily tested on synthetic samples of trimethylamine (TMA), dimethylamine (DMA), methylamine (MA) and ammonia (i.e. the main species responsible for the typical flavor of spoiled fish), thus verifying that only TMA, DMA and MA can be detected because NH₃ oxidation occurred beyond the solvent discharge. This notwithstanding, detection of the sole TMA, DMA and MA as a whole turned out to be well suited for the rapid assessment of fish spoilage, since during storage the release enhancement for these amines is largely predominant over that of NH₃. Repeatable (8 % RSD) sharp peaks were detected for all amines above over a wide range (5–1000 nmol) and a detection limit of a little more than 3 nmol was inferred for a signal‐to‐noise ratio of 3. This approach was applied to the detection of VAs released from real fish samples (sardines), in parallel to the determination of their total volatile basic nitrogen (TVBN), which is a conventional indicator frequently adopted for the chemical quality assessment of fish. A substantially satisfactory agreement was found by comparing the data achieved by these two approaches.     

Purification and stability of glutaryl-7-ACA acylase from pseudomonas sp.

The enzyme glutaryl-7-ACA acylase fromPseudomonas sp. NCIMB 40474, produced by a recombinantEscherichia coli host, was purified to homogeneity. The enzyme is a tetramer composed of two couples of asymmetric dimers, each of them constituted of two subunits of mol wt 18 and 52 kDa, respectively. It was found that glutaric acid, one of the products of the substrate hydrolysis, is an effective acylase inhibitor. Between pH 6.0 and pH 10.0, the enzymatic activity is almost constant, but below pH 6.0 it progressively declines. The acylase activity decreased sharply as a function of guanidine HC1 concentration. The loss is significant even at concentrations of denaturant lower than those causing unfolding, as suggested by UV spectroscopy and fluorescence emission studies. In these conditions (low denaturant concentration and low pH) the inactivation of the enzyme is caused by the tetramer dissociation into dimers. The lability of the quaternary structure of the enzyme is a key feature that must be taken into account for the improvement of the catalyst stability.     

Mathematics Teaching in Italy: A Cross-Cultural Video Analysis

This study investigates the cultural nature of teaching. It compares a sample of 39 videotaped Italian mathematics lessons to German, Japanese, and U.S. lessons videotaped in TIMSS. This study expands on earlier work that was based on a smaller sample; analysis is also extended to the nature of the mathematical content presented. The results confirm the existence of an Italian cultural pattern for mathematics teaching, whose features we outline here. Italian teachers prefer whole-class instruction to individual seatwork; they engage in teacher talk/demonstration to transmit information; and they often call on students to solve problems at the board before the rest of the class. Italian lessons are characterized by the inclusion of a large number of mathematical principles and properties. These are explained 50% of the time, and simply stated the rest of the time. This study adds yet another perspective from which mathematics teaching can be studied, and, by acknowledging the difficulty to change cultural practices, it offers practical implications for teacher learning.     

Capillary zone electrophoresis (CZE) coupled to time-of-flight mass spectrometry (TOF-MS) applied to the analysis of illicit and controlled drugs in blood

A new method for the determination of illicit and abused drugs in blood by capillary zone electrophoresis-electrospray ionization-time-of-flight mass spectrometry is proposed, in view of its application in clinical and forensic toxicology. The analytes (methamphetamine, methylenedioxyamphetamine, methylenedioxyethylamphetamine, methylenedioxymethamphetamine, methadone, cocaine, morphine, codeine, 6-acethylmorphine, benzoylecgonine) were separated with capillary zone electrophoresis by applying 15 kV within 25 min, in an uncoated fused-silica capillary (75 microm x 100 cm) using a 25 mM ammonium formate electrolyte solution (pH 9.5). The capillary electropherograph was coupled to time-of-flight mass spectrometry through an orthogonal electrospray ionization source, with a coaxial sheath liquid interface. The sheath liquid was composed of isopropanol-water (1:1 v/v) containing 0.5% formic acid delivered at 4 microL/min. Forensic drugs were identified by exact mass determination (mass accuracy typically < or =5 ppm) and by matching of the isotopic pattern. Under optimized conditions, linearity was assessed in the range 10-2000 ng/mL, with correlation coefficients between 0.9744 and 0.9982 for all the analytes. LODs were in the range of 2-10 ng/mL (S/N > or =3) and LOQs of 10-30 ng/mL. The CVs (tested at 40 and 800 ng/mL in biological matrix) were below 2.97% for migration times and below 14.61% for peak area ratios (analyte/internal standard). Blood samples were extracted by using a liquid-liquid extraction procedure and injected under field-amplified sample stacking conditions. The method was successfully applied to real cases.     

Mechanism of indium(III) exchange between NTA and transferrin: a kinetic approach

The equilibria and kinetics for the process of In(3+) exchange between nitrilotriacetic acid (NTA) and bovine serum transferrin (T) have been investigated in aqueous solution containing sodium bicarbonate. The metal exchange equilibria have been measured by difference ultraviolet spectroscopy at 25 degrees C, pH=7.4, and I=0.2 M (NaClO4). The acid dissociation constants of NTA and the binding constants of In(III) to NTA have also been measured. Kinetic experiments revealed that the process of In(3+) uptake by transferrin from [In(NTA)2](3-) is biphasic, the fast phase being completed in a few seconds, the slow phase lasting for hours. The fast phase has been investigated by the stopped-flow method and results in monoexponential kinetics. It involves rapid interaction of the 1:1 complex ML (M=In, L=NTA) with TB (T=transferrin, B=CO3(2-)) to give a quaternary intermediate MLTB which then evolves to an "open" MTB* ternary complex complex with expulsion of L. In turn, this complex interconverts to a "closed", more stable, form MTB. Neither the prevailing complex M2L nor the TB2 form of transferrin are directly involved in the exchange process but act as metal and protein reservoirs. The pH dependence of the reaction has been also investigated. The slow phase has not been investigated in detail; it takes several hours to go to the completeness, its slowness being ascribed to metal redistribution between the C-site and N-site of the protein, and/or metal release from polynuclear In(III) species.     

Self‐(Un)rolling Biopolymer Microstructures: Rings,Tubules, and Helical Tubules from the Same Material

We have demonstrated the facile formation of reversible and fast self‐rolling biopolymer microstructures from sandwiched active–passive, silk‐on‐silk materials. Both experimental and modeling results confirmed that the shape of individual sheets effectively controls biaxial stresses within these sheets, which can self‐roll into distinct 3D structures including microscopic rings, tubules, and helical tubules. This is a unique example of tailoring self‐rolled 3D geometries through shape design without changing the inner morphology of active bimorph biomaterials. In contrast to traditional organic‐soluble synthetic materials, we utilized a biocompatible and biodegradable biopolymer that underwent a facile aqueous layer‐by‐layer (LbL) assembly process for the fabrication of 2D films. The resulting films can undergo reversible pH‐triggered rolling/unrolling, with a variety of 3D structures forming from biopolymer structures that have identical morphology and composition.     

A chromatographic study on the exceptional enantioselectivity of cellulose tris(4-methylbenzoate) towards C5-chiral 4,5-dihydro-(1H)-pyrazole derivatives

A set of ten C5-chiral 4,5-dihydro-(1H)-pyrazole derivatives was synthesized and analyzed by high-performance liquid chromatography (HPLC) on the polysaccharide-based Chiralcel OJ-H chiral stationary phase (CSP). The enantioseparations were carried out using pure ethanol as eluent. Different structural elements of the investigated compounds were recognized for obtaining a very high enantioselectivity. In order to clarify some aspects of the chiral discrimination process, the thermodynamic parameters associated to the enantiorecognition and the enantiomer elution order were established.     

Permeability and micromechanical properties of silk ionomer microcapsules

We studied the pH-responsive behavior of layer-by-layer (LbL) microcapsules fabricated from silk fibroin chemically modified with different poly amino acid side chains: cationic (silk-poly l-lysine, SF-PL) or anionic (silk-poly-l-glutamic acid, SF-PG). We observed that stable ultrathin shell microcapsules can be assembled with a dramatic increase in swelling, thickness, and microroughness at extremely acidic (pH < 2.5) and basic (pH > 11.0) conditions without noticeable disintegration. These changes are accompanied by dramatic changes in shell permeability with a 2 orders of magnitude increase in the diffusion coefficient. Moreover, the silk ionomer shells undergo remarkable softening with a drop in Young's modulus by more than 1 order of magnitude due to the swelling, stretching, and increase in material porosity. The ability to control permeability and mechanical properties over a wide range for the silk-based microcapsules, with distinguishing stability under harsh environmental conditions, provides an important system for controlled loading and release and applications in bioengineering.