A New Bi-Functional Derivative of Polyethylene Glycol as Molecular Carrier for Eugenol and Ibuprofen

Eugenol (EU) and ibuprofene (IBU) were covalently bound to a bi-functionalized PEG, used as molecular carrier of drugs and the release kinetics of the two bioactive molecules was studied in vitro in buffer solution at pH 7.4, in simulated gastric fluid and in mouse plasma. The hydrolysis studies showed a specific cleavage dependent on the pH of the medium and by the presence of proteolytic enzymes in mouse plasma. Studies in vitro on the release of the parent drug from this double prodrug in various media, indicate that the adduct may be sufficiently stable to pass intact the gastrointestinal tract and release into the circulation EU and IBU. Many advantages may be achieved by the synthesis of the prodrug EU-PEG-IBU related to synergistic analgesic and anti-inflammatory effects, to the reduction of the adverse reactions and the improvement of the chemical-physical properties of the parent drugs

An Easy Route to Enantiomerically Enriched 7- and 8-Hydroxystearic Acids by Olefin Metathesis - Based Approach

The synthesis of enantiomerically enriched 7- and 8-hydroxystearic acids (7- and 8-HSA) has been successfully accomplished starting from chiral non racemic 1-pentadecen-4-ol and 1-tetradecen-4-ol respectively. Their Yamaguchi\u2019s esterification with 4-pentenoic and 5-hexenoic acids respectively afforded the suitable dienic esters which were submitted to ring closing metathesis reaction. After hydrogenation and basic hydrolysis of the complex reaction mixture, chiral non racemic 7- and 8-HSA were obtained in about 40% total yield

An alternative encapsulation approach for production of active chitosan-propolis beads

Encapsulation is a promising technology to carry natural active substances, preventing their loss and maintaining their stability until use. Beads of chitosan-containing propolis have been prepared using a mono-pore filter device, which permits the encapsulation of natural polyphenols avoiding heat treatments, high shear rates and the use of toxic solvents. Beads proved to be active against Bacillis cereus, Escherichia coli, Listeria innocua, Pseudomonas fluorescens, Yarrovia lipolytica and three moulds strains; the highest effect was found against Staphylococcus aureus (MIC 0.8 mg beads mL-1). Results in liquid cultures of S. aureus evidenced that beads were able to release the flavonoids from propolis: the diffusion of the active compounds is a key factor in the exploitation of the microbial activity. The obtained chitosan-propolis beads represent an example of natural antimicrobial delivery system that could be used to prevent the growth of pathogenic/spoilage bacteria in food applications

Carrier-Induced Magnetic Circular Dichloism in the Magnetoresistive Pyrochlore Tl2Mn2O7

Infrared magnetic circular dichloism (MCD), or equivalently magneto-optical Kerr effect, has been measured on the Tl2Mn2O7 pyrochlore, which is well known for exhibiting a large magnetoresistance around the Curie temperature T_C ~ 120 K. A circularly polarized, infrared synchrotron radiation is used as the light source. A pronounced MCD signal is observed exactly at the plasma edge of the reflectivity near and below T_c. However, contrary to the conventional behavior of MCD for ferromagnets, the observed MCD of Tl2Mn2O7 grows with the applied magnetic field, and not scaled with the internal magnetization. It is shown that these results can be basically understood in terms of a classical magnetoplasma resonance. The absence of a magnetization-scaled MCD indicates a weak spin-orbit coupling of the carriers in Tl2Mn2O7. We discuss the present results in terms of the microscopic electronic structures of Tl2Mn2O7.Comment: 5 pages, 5 figures, submitted to J. Phys. Soc. Jp

Experimental evaluation of the thermal polarization in direct contact membrane distillation using electrospun nanofiber membranes doped with molecular probes

Membrane distillation (MD) has recently gained considerable attention as a valid process for the production of fresh-water due to its ability to exploit low grade waste heat for operation and to ensure a nearly feed concentration-independent production of high-purity distillate. Limitations have been related to polarization phenomena negatively affecting the thermal efficiency of the process and, as a consequence, its productivity. Several theoretical models have been developed to predict the impact of the operating conditions of the process on the thermal polarization, but there is a lack of experimental validation. In this study, electrospun nanofiber membranes (ENMs) made of Poly(vinylidene fluoride) (PVDF) and doped with (1, 10-phenanthroline) ruthenium (II) Ru(phen) 3 were tested at different operating conditions (i.e., temperature and velocity of the feed) in direct contact membrane distillation (DCMD). The temperature sensitive luminophore, Ru(phen) 3 , allowed the on-line and non-invasive mapping of the temperature at the membrane surface during the process and the experimental evaluation of the effect of the temperature and velocity of the feed on the thermal polarization

Enhancing proteotoxic stress in leiomyosarcoma cells triggers mitochondrial dysfunctions, cell death, and antitumor activity in vivo

Leiomyosarcomas are rare and aggressive tumors characterized by a complex karyotype. Surgical resection with or without radiotherapy and chemotherapy is the standard curative treatment. Unfortunately, a high percentage of leiomyosarcomas recurs and metastasizes. In these cases, doxorubicin and ifosfamide represent the standard treatment but with low response rates. Here, we evaluated the induction of proteotoxic stress as a possible strategy to kill leiomyosarcoma cells in a therapeutic perspective. We show that aggressive leiomyosarcomas coexist with high levels of proteotoxic stress. As a consequence, we hypothesized that leiomyosarcoma cells are vulnerable to further increases of proteotoxic stress. The small compound 2c is a strong inducer of proteotoxic stress. In leiomyosarcoma cells, it triggers cell death coupled to a profound reorganization of the mitochondrial network. By using stimulated emission depletion microscopy, we have unveiled the existence of DIABLO/SMAC clusters that are modulated by 2c. Finally, we have engineered a new version of 2c linked to polyethylene glycol though a short peptide, named 2cPP. This new prodrug is specifically activated by proteases present in the tumor microenvironment. 2cPP shows a strong antitumor activity in vivo against leiomyosarcomas and no toxicity against normal cells

A non-invasive optical method for mapping temperature polarization in direct contact membrane distillation

Membrane Distillation (MD) is a thermal membrane process allowing for a theoretical 100% rejection of non-volatile compounds (i.e. ions, macromolecules, colloids, cells), whereas vapour molecules permeate through a micro-porous hydrophobic membrane due to a difference of vapour pressure established across the membrane-self. The effective driving force and, then, the vapour trans-membrane flux is affected by temperature polarization phenomena occurring in the boundary layers adjacent to the membrane. The temperature values at the membrane surface are usually difficult to measure and only recently some invasive techniques were adopted for this scope. The aim of this work was to introduce luminescent molecular probing as an innovative technology for non-invasive and in-situ monitoring of thermal polarization in MD. Tris(phenantroline)ruthenium(II) chloride (Ru(phen)3) was selected as temperature sensitive luminescent probe and immobilized in a flat poly(vinylidene fluoride) electrospun nanofibrous membrane (PVDF ENM). Experiments showed the key role of the Ru(phen)3 and Lithium Chloride (LiCl) in the preparation of homogeneous PVDF ENM due to their ionic nature that improved the electrical conductivity of the polymeric solution favouring the electrospinning. Furthermore, PVDF ENM showed a good performance in Direct Contact Membrane Distillation (DCMD) process. The immobilization of the molecular probe allowed to optically monitoring the membrane surface temperature during DCMD experiments. On the other hand, the employment of an IR-camera permitted the evaluation of the temperature of the bulk of liquid streams. Therefore, the combination of these two optical techniques enabled to evaluate, in a direct and non-invasive way, the thermal polarization along the membrane module during DCMD experiments

Low-cost inorganic cation exchange membrane for electrodialysis: optimum processing temperature for the cation exchanger

The optimum temperature for fixing zirconium phosphate, obtained by precipitation, on a low-cost ceramic support was determined in order to obtain an inorganic cation exchange membrane for electrodialysis. Zirconium phosphate ion exchange capacity maximised between 450 and 550°C, thus it was considered the optimum processing temperature. The origin of this maximum was investigated by means of X-ray diffraction and termogravimetry and evolved gas analysis. Zirconium phosphate formation by precipitation in the porous network of the support was verified by scanning electron microscopy and energy dispersive X-ray analysis and mercury intrusion porosimetry. The membrane obtained after thermal treatment at 450°C displayed selectivity to the cations present in the spent rinse water of the chromium plating process. This property allows the recovery of chromium by removing the cations through the cation exchange ceramic membrane.The authors wish to express their gratitude to the Spanish Ministry of Science and Innovation for the support given to the research study (National Basic Research Programme, Ref. CTQ2008-06750-C02-02), as well as for the FPU student grant awarded to one of the authors (Ref.: AP2009-4409).Mestre, S.; Sales, S.; Palacios, M.; Lorente, M.; Mallol, G.; Pérez-Herranz, V. (2013). Low-cost inorganic cation exchange membrane for electrodialysis: optimum processing temperature for the cation exchanger. Desalination and Water Treatment. 51(16-18):3317-3324. https://doi.org/10.1080/19443994.2012.749177S331733245116-18Strathmann, H. (2010). Electromembrane Processes: Basic Aspects and Applications. Comprehensive Membrane Science and Engineering, 391-429. doi:10.1016/b978-0-08-093250-7.00048-7Drioli, E., & Fontananova, E. (s. f.). Integrated Membrane Processes. 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