NSAID-Based Coordination Compounds for Biomedical Applications: Recent Advances and Developments

After the serendipitous discovery of cisplatin, a platinum-based drug with chemotherapeutic effects, an incredible amount of research in the area of coordination chemistry has been produced. Other transition metal compounds were studied, and several new relevant metallodrugs have been synthetized in the past few years. This review is focused on coordination compounds with first-row transition metals, namely, copper, cobalt, nickel or manganese, or with zinc, which have potential or effective pharmacological properties. It is known that metal complexes, once bound to organic drugs, can enhance the drugs’ biological activities, such as anticancer, antimicrobial or anti-inflammatory ones. NSAIDs are a class of compounds with anti-inflammatory properties used to treat pain or fever. NSAIDs’ properties can be strongly improved when included in complexes using their compositional N and O donor atoms, which facilitate their coordination to metal ions. This review focuses on the research on this topic and on the promising or effective results that complexes of first-row transition metals and NSAIDs can exhibit.     

CD8+ T Cell Senescence: Lights and Shadows in Viral Infections,Autoimmune Disorders and Cancer

CD8⁺ T lymphocytes are a heterogeneous class of cells that play a crucial role in the adaptive immune response against pathogens and cancer. During their lifetime, they acquire cytotoxic functions to ensure the clearance of infected or transformed cells and, in addition, they turn into memory lymphocytes, thus providing a long-term protection. During ageing, the thymic involution causes a reduction of circulating T cells and an enrichment of memory cells, partially explaining the lowering of the response towards novel antigens with implications in vaccine efficacy. Moreover, the persistent stimulation by several antigens throughout life favors the switching of CD8⁺ T cells towards a senescent phenotype contributing to a low-grade inflammation that is a major component of several ageing-related diseases. In genetically predisposed young people, an immunological stress caused by viral infections (e.g., HIV, CMV, SARS-CoV-2), autoimmune disorders or tumor microenvironment (TME) could mimic the ageing status with the consequent acceleration of T cell senescence. This, in turn, exacerbates the inflamed conditions with dramatic effects on the clinical progression of the disease. A better characterization of the phenotype as well as the functions of senescent CD8⁺ T cells can be pivotal to prevent age-related diseases, to improve vaccine strategies and, possibly, immunotherapies in autoimmune diseases and cancer.     

Effect of different temperature–time combinations on physicochemical,microbiological, textural and structural features of sous-vide cooked lamb loins

Lamb loins were subjected to sous-vide cooking at different combinations of temperature (60, 70, and 80 °C) and time (6, 12, and 24 h). Different physicochemical, histological and structural parameters were studied. Increasing cooking temperatures led to higher weight losses and lower moisture contents, whereas the effect of cooking time on these variables was limited. Samples cooked at 60 °C showed the highest lightness and redness, while increasing cooking temperature and cooking time produced higher yellowness values. Most textural variables in a texture profile analysis showed a marked interaction between cooking temperature and time. Samples cooked for 24 h showed significantly lower values for most of the studied textural parameters for all the temperatures considered. Connective tissue granulation at 60 °C and gelation at 70 °C were observed in the SEM micrographs. The sous-vide cooking of lamb loins dramatically reduced microbial population even with the less intense heat treatment studied (60 °C–6 h).     

Development of molecularly imprinted co-polymeric devices for controlled delivery of flufenamic acid using supercritical fluid technology

This work reports the development of a novel class of affinity co-polymeric materials using supercritical fluid technology. Polymeric materials with molecular recognition to flufenamic acid, were first synthesized in supercritical carbon dioxide (scCO₂) using the drug as template. Molecularly imprinted co-polymers of methacrylic acid (MAA) or N-isopropyl acrylamide (NIPAAm) crosslinked with ethylene glycol dimethacrylate (EGDMA) were synthesized using different crosslinking degrees and template:monomer ratios, at 65 °C and 21 MPa. High-pressure NMR experiments confirmed that the nature of the interactions between the drug and the functional monomers during the polymerization step are mainly hydrogen bonds. scCO₂-assisted impregnation revealed that the imprinted matrices were able to uptake higher amounts of flufenamic acid. This effect was particularly evidenced in the more crosslinked matrices, with P(MAA-EGDMA) imprinted copolymers binding up to 101.5 mg drug/g polymer against only 50.5 mg/g in the non-imprinted copolymer. In vitro drug delivery experiments showed that imprinted co-polymers release the drug in a more sustained way than the corresponding non-imprinted matrices. Overall it was shown that supercritical fluid technology is a viable approach for the development of self-assembly molecular recognition polymers with potential application in controlled drug delivery systems.     

Spray-dried high-amylose sodium carboxymethyl starch: impact of α-amylase on drug-release profile

Spray-dried high-amylose sodium carboxymethyl starch (SD HASCA) is a promising pharmaceutical excipient for sustained-release (SR) matrix tablets produced by direct compression. The presence of α-amylase in the gastrointestinal tract and the variations of the gastric residence time of non-disintegrating dosage forms may affect the presystemic metabolism of this excipient and, consequently, the drug-release profile from formulations produced with SD HASCA. In this study, the influence of α-amylase and the residence time in acidic conditions on the drug-release profile was evaluated for a once-daily acetaminophen formulation (Acetaminophen SR) and a once-daily tramadol hydrochloride formulation (Tramadol SR). Both formulations were based on SD HASCA. α-Amylase concentrations ranging from 0?IU/L to 20000?IU/L did not significantly affect the drug-release profiles of acetaminophen and tramadol hydrochloride from SD HASCA tablets (f_2?>_?50) for all but only one of the studied conditions (f_2?=_?47). Moreover, the drug-release properties from both SD HASCA formulations were not significantly different when the residence time in acidic medium was 1?h or 3?h. An increase in α-amylase concentration led to an increase in the importance of polymer erosion as the main mechanism of drug-release instead of drug diffusion, for both formulations and both residence times, even if release profiles remained comparable. As such, it is expected that α-amylase concentration and residence time in the stomach will not clinically affect the performance of both SD HASCA SR formulations, even if the mechanism of release itself may be affected.     

Physicochemical properties and quality parameters of herbhoneys

Herbhoney is a honey-like substance produced by bees fed on a saccharose-based food supplemented with herbal extracts or fruit juices. Having specific sensory characteristics (colour, aroma and taste), different from those of natural honeys, herbhoneys greatly extend the range of bee products. With the aim of improving the knowledge of herbhoneys of various origins, their chosen physicochemical and quality parameters were evaluated. It was found that the herbhoneys studied satisfied most of the requirements relative to natural honeys (water, hydroxymethylfurfural and saccharose contents, free acidity, and diastase number). Some of the samples showed an increased specific conductivity, characteristic of honeydew honeys, although the ash contents of herbhoneys were at a level typical of nectar honeys. The saccharose content of some herbhoneys exceeded the value allowed for most natural honeys. Mineral composition varied between the samples, being in most cases within the limits reported in this literature for natural honeys.     

Study of hydroxycinnamic acids and malvidin 3-monoglucoside derivatives using capillary zone electrophoresis and ultra-performance liquid chromatography

Model solutions (pH = 3.5, 12% ethanol) of malvidin 3-O-glucoside (Mv3glc), the most common free anthocyanin in grapes and red wines from Vitis vinifera, and three free hydroxycinnamic acids present in wines (caffeic, ferulic and p-coumaric acids) were studied.     

Selection of a cleaning system for engine maintenance based on the analytic hierarchy process

Environmental impact assessment is an intrinsically complex multi-dimensional process which involves multiple criteria and multiple actors. Multi-criteria methods can serve as useful decision aids for carrying out environmental impact assessment. This paper proposes the use of a multi-criteria technique, namely the analytic hierarchy process, as a potential decision-making method for use in management maintenance processes. In this case, our problem concerns the selection of a parts cleaning system for diesel engine maintenance. A hierarchical structure is built for the prequalification of the criteria and the alternatives within the system. By applying the analytic hierarchical process, the criteria can be prioritized and the alternatives can be organized in descending order so that the best parts cleaning system may be selected.     

Development of pH-responsive poly(methylmethacrylate-co-methacrylic acid) membranes using scCO2 technology. Application to protein permeation

Porous membranes were developed in a two step process using supercritical CO₂ technology. Copolymers of methyl methacrylate (MMA) and methacrylic acid (MAA) were synthesized for the first time in supercritical carbon dioxide (scCO₂), being identified by ¹H NMR and FT-IR. The influence of the feed monomer ratio on their morphology, average molecular weight and T_g was studied. These PMMA-co-PMAA copolymers were then used in the preparation of thin pH-responsive membranes by scCO₂-assisted phase inversion method. The prepared films were characterized by scanning electron microscopy, mercury porosimetry, dynamical mechanical analysis, swelling and contact angle measurements, in order to study their morphology, pH-responsive character, hydrophilicity and viscoelastic properties by changing the monomer ratio composition of the copolymer from 5 to 50 wt% of MAA with respect to the total mass of monomers. PMMA-co-PMAA membranes were then tested for a potential application as protein filtration devices. Bovine serum albumin (BSA) was used as a model protein and permeation measurements were performed at three different pHs (4.5, 5.0 and 7.4). The PMMA–PMAA (90:10) membrane showed a good performance in terms of BSA amount filtrated, with distinct profiles at different pH, and consequently capable to assume an efficient role in protein filtration processes.