Widespread detection of chlorine oxyacids in the Arctic atmosphere

Chlorine radicals are strong atmospheric oxidants known to play an important role in the depletion of surface ozone and the degradation of methane in the Arctic troposphere. Initial oxidation processes of chlorine produce chlorine oxides, and it has been speculated that the final oxidation steps lead to the formation of chloric (HClO3) and perchloric (HClO4) acids, although these two species have not been detected in the atmosphere. Here, we present atmospheric observations of gas-phase HClO3 and HClO4. Significant levels of HClO3 were observed during springtime at Greenland (Villum Research Station), Ny-Ålesund research station and over the central Arctic Ocean, on-board research vessel Polarstern during the Multidisciplinary drifting Observatory for the Study of the Arctic Climate (MOSAiC) campaign, with estimated concentrations up to 7 × 106 molecule cm−3. The increase in HClO3, concomitantly with that in HClO4, was linked to the increase in bromine levels. These observations indicated that bromine chemistry enhances the formation of OClO, which is subsequently oxidized into HClO3 and HClO4 by hydroxyl radicals. HClO3 and HClO4 are not photoactive and therefore their loss through heterogeneous uptake on aerosol and snow surfaces can function as a previously missing atmospheric sink for reactive chlorine, thereby reducing the chlorine-driven oxidation capacity in the Arctic boundary layer. Our study reveals additional chlorine species in the atmosphere, providing further insights into atmospheric chlorine cycling in the polar environmentNational Natural Science Foundation of China (42175118)European Research Council Executive Agency under the European Union’s Horizon 2020 Research and Innovation Program (Project ERC-2016-COG726349 CLIMAHAL, ERC-StG GASPARCON - grant agreement no. 714621The EMME-CARE project – grant agreement no. 856612, and grant no. 101002728, ATM-GTP Contract No. 742206)Climate Relevant interactions and feedbacks: the key role of sea ice and Snow in the polar and global climate system(CRiceS, grant number 101003826)Horizon Europe project Non-CO2 Forcers and their Climate, Weather, Air Quality and Health Impacts, (FOCI, project number 101056783)ACCC Flagship funded by the Academy of Finland grant no. 337549Academy professorship funded by the Academy of Finland (grant no. 302958Academy of Finland (project nos. 296628, 328290, 311932, 316114, 325647, 325681, 334792, 337549, 329274, 333397, 328616, 1325656, 347782, 349659, and 334514)Academy of Finland (project nos. 296628, 328290, 311932, 316114, 325647, 325681, 334792, 337549, 329274, 333397, 328616, 1325656, 347782, 349659, and 334514)United States National Science Foundation (grant nos. 1807496 and 1807163),Swiss National Science Foundation (grant 200021_188478)Swiss Polar Institute (grant no. DIRCR-2018-004The Ingvar Kamprad Chair for Extreme Environments Research, sponsored by Ferring PharmaceuticalsLa Caixa” Foundation (ID 100010434) for the fellowship LCF/BQ/DR20/11790027Spanish “Ministerio de Ciencia e Innovación (MICINN)” for funding (Project ref. CTQ2017-87054-C2-2-P,Unit of Excellence María de Maeztu CEX2019-000919-M and “Ramón y Cajal” grant RYC- 2015-19234International Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) expedition with the MOSAiC20192020 tag, with activities supported by Polarstern76 expedition AWI_PS122_00National Oceanic and Atmospheric Administration (NOAA) Air Resources Laboratory (ARL) for the provision of the Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) transport and dispersion model and/or Real-time Environmental Applications and Display sYstem (READY

Molecular Modeling of Adsorption of 5-Aminosalicylic Acid in the Halloysite Nanotube

Halloysite nanotubes are becoming interesting materials for drug delivery. The knowledge of surface interactions is important for optimizing this application. The aim of this work is to perform a computational study of the interaction between 5-aminosalicylic acid (5-ASA) drug and halloysite nanotubes for the development of modified drug delivery systems. The optimization of this nanotube and the adsorption of different conformers of the 5-ASA drug on the internal surface of halloysite in the presence and absence of water were performed using quantum mechanical calculations by using Density Functional Theory (DFT) and methods based on atomistic force fields for molecular modeling, respectively.This work is funded by the Andalusian Government projects (RNM1897) and the MINECO project FIS2016-77692-C2-2P. It also supported by the Egyptian Cultural Affairs and Missions Sector (Plan 2013-2014), Ministry of Higher Education

Theoretical Study of Retinol, Niacinamide and Glycolic Acid with Halloysite Clay Mineral as Active Ingredients for Topical Skin Care Formulations

This research was funded by Spanish Ministerio de Economia, Industria y Competitividad, grant number PCIN2017-098, and by Regional Government Junta de Andalucia with FEDER European contribution, grant number P18-RT-3786.The adsorption of retinol, niacinamide and glycolic acid active ingredients on the internal surface of halloysite in an aqueous environment was explored at the molecular level by means of calculations based on quantum mechanics and force fields from empirical interatomic potentials. These active ingredients are stably adsorbed on the internal surface of halloysite forming hydrogen bonds between the hydrogen, oxygen and nitrogen atoms with the hydroxyl groups of the inner surface of the halloysite. In addition, electrostatic interaction between these active ingredients with the water molecules was observed. Therefore, the theoretical results indicate that the adsorption of these active principles is favourable in the halloysite nanotube, which allows directing future experimental investigations for the development and design of retinol, niacinamide and glycolic acid with halloysite nanotubes systems, which may be topical formulations for skincare.Spanish Ministerio de Economia, Industria y Competitividad PCIN2017-098Junta de AndaluciaEuropean Commission P18-RT-378

Wound Healing Activity of Nanoclay/Spring Water Hydrogels

This project was supported by an FPU grant (MECD), the Spanish research group CTS-946 and the program for international mobility of PhD students (University of Granada). Special thanks to the Department of Drug Sciences of the University of Pavia (Italy).Background: hydrogels prepared with natural inorganic excipients and spring waters are commonly used in medical hydrology. Design of these clay-based formulations continues to be a field scarcely addressed. Safety and wound healing properties of different fibrous nanoclay/spring water hydrogels were addressed. Methods: in vitro biocompatibility, by means of MTT assay, and wound healing properties were studied. Confocal Laser Scanning Microscopy was used to study the morphology of fibroblasts during the wound healing process. Results: all the ingredients demonstrated to be biocompatible towards fibroblasts. Particularly, the formulation of nanoclays as hydrogels improved biocompatibility with respect to powder samples at the same concentration. Spring waters and hydrogels were even able to promote in vitro fibroblasts motility and, therefore, accelerate wound healing with respect to the control. Conclusion: fibrous nanoclay/spring water hydrogels proved to be skin-biocompatible and to possess a high potential as wound healing formulations. Moreover, these results open new prospects for these ingredients to be used in new therapeutic or cosmetic formulations.German Research Foundation (DFG)Spanish research group CTS-946Program for international mobility of PhD students (University of Granada

Praziquantel–Clays as Accelerated Release Systems to Enhance the Low Solubility of the Drug

Praziquantel is an antiparasitic drug indicated for the treatment of the schistosomiasis disease. This drug has very low aqueous solubility, requiring high oral doses for its administration which gives rise to side effects, therapeutic noncompliance and the appearance of resistant forms of the parasite. Clay minerals, like sepiolite and montmorillonite, are innocuous, non-toxic, biocompatible and low-cost excipients. Additionally, clays have high adsorbent properties that allow them to encapsulate drugs in nanometric spaces present in the channels in the case of the sepiolite or between the layers in the case of the montmorillonite. The interactions between the drug and clay minerals are studied experimentally with the strategy for preparing interactions products in organic solvents (ethanol, acetonitrile and dichloromethane) so that the interaction will be more effective and will be enhanced the aqueous solubility of praziquantel. The results showed that in the interaction products, the drug interacted with both clay minerals, which produced the loss of the crystallinity of the drug demonstrated by different techniques. This led to a significant increase in the dissolution rate of the praziquantel in all the interaction products in the simulated gastrointestinal tract media, except for the praziquantel–montmorillonite product prepared in dichloromethane that presented a controlled release in acid medium. Moreover, in vitro cytotoxicity and cell cycle studies were performed in the interaction products prepared with ethanol. The interaction product with sepiolite was biocompatible with the HTC116 line cells, and it did not produce alterations in the cell cycle. However, interaction products with montmorillonite did not produce cell death, but they showed affectation and damage of cells in the cell cycle study at the highest concentration tested (20–100 µM). Therefore, the different organic solvents used are adequate for the improvement of the biopharmaceutical profile of praziquantel. Drug–clay interaction products, specifically with sepiolite, showed very promising results in which new accelerated oral release systems of the praziquantel were obtained.Ministerio de Ciencia e Innovacion government PCIN-2017-098 FIS2016-77692-C2-2-P CGL2016-80833-RJunta de Andalucia RNM1897 P18-RT-378

The Effect of the Presence of Amino Acids on the Precipitation of Inorganic Chemical-Garden Membranes: Biomineralization at the Origin of Life

If life developed in hydrothermal vents, it would have been within mineral membranes. The first proto-cells must have evolved to manipulate the mineral membranes that formed their compartments in order to control their metabolism. There must have occurred a biological takeover of the self-assembled mineral structures of the vents, with the incorporation of proto-biological molecules within the mineral membranes to alter their properties for life’s purposes. Here, we study a laboratory analogue of this process: chemical-garden precipitation of the amino acids arginine and tryptophan with the metal salt iron chloride and sodium silicate. We produced these chemical gardens using different methodologies in order to determine the dependence of the morphology and chemistry on the growth conditions, as well as the effect of the amino acids on the formation of the iron-silicate chemical garden. We compared the effects of having amino acids initially within the forming chemical garden, corresponding to the internal zones of hydrothermal vents, or else outside, corresponding to the surrounding ocean. The characterization of the formed chemical gardens using X-ray diffraction, Fourier transform infrared spectroscopy, elemental analysis, and scanning electron microscopy demonstrates the presence of amino acids in these structures. The growth method in which the amino acid is initially in the tablet with the iron salt is that which generated chemical gardens with more amino acids in their structures.European Commission P-18-RT-3786Spanish Andalusian CA1712

Tablets of “Hydrochlorothiazide in Cyclodextrin in Nanoclay”: A New Nanohybrid System with Enhanced Dissolution Properties

Hydrochlorothiazide (HCT), a Biopharmaceutical Classification System (BCS) class IV drug, is characterized by low solubility and permeability, that negatively affect its oral bioavailability, reducing its therapeutic effcacy. The combined use of cyclodextrins (CDs) and nanoclays (NCs) recently proved to be a successful strategy in developing delivery systems able to merge the potential benefits of both carriers. In this work, several binary systems of CDs or NCs with the drug were obtained, using different drug:carrier ratios and preparation techniques, and characterized in solution and in solid state, to properly select the most effective system and preparation method. Then, the best CD (RAMEB) and NC (sepiolite), at the best drug:carrier ratio, was selected for preparation of the ternary system by co-evaporation and emerged as the most effective preparation method. The combined presence of RAMEB and sepiolite gave rise to a synergistic improvement of drug dissolution properties, with a two-fold increase in the amount of drug dissolved as compared with the corresponding HCT-RAMEB system, resulting in an approximately 12-fold increase in drug solubility as compared with the drug alone. The ternary system that was co-evaporated was then selected for a tablet formulation. The obtained tablets were fully characterized for technological properties and clearly revealed a better drug dissolution performance than the commercial reference tablet (Esidrex®)

Wound Healing Activity of Nanoclay/Spring Water Hydrogels

Background: hydrogels prepared with natural inorganic excipients and spring waters are commonly used in medical hydrology. Design of these clay-based formulations continues to be a field scarcely addressed. Safety and wound healing properties of different fibrous nanoclay/spring water hydrogels were addressed. Methods: in vitro biocompatibility, by means of MTT assay, and wound healing properties were studied. Confocal Laser Scanning Microscopy was used to study the morphology of fibroblasts during the wound healing process. Results: all the ingredients demonstrated to be biocompatible towards fibroblasts. Particularly, the formulation of nanoclays as hydrogels improved biocompatibility with respect to powder samples at the same concentration. Spring waters and hydrogels were even able to promote in vitro fibroblasts motility and, therefore, accelerate wound healing with respect to the control. Conclusion: fibrous nanoclay/spring water hydrogels proved to be skin-biocompatible and to possess a high potential as wound healing formulations. Moreover, these results open new prospects for these ingredients to be used in new therapeutic or cosmetic formulations.This research was funded by Ministerio de Ciencia e Innovación, CGL2016–80833-R; Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía, P18-RT-3786 and Ministerio de Educación, Cultura y Deporte, FPU15/01577.Peer reviewe

Ground Calcium Carbonate as a Low Cost and Biosafety Excipient for Solubility and Dissolution Improvement of Praziquantel

Calcium carbonate is an abundant mineral with several advantages to be a successful carrier to improve oral bioavailability of poorly water-soluble drugs, such as praziquantel. Praziquantel is an antiparasitic drug classified in group II of the Biopharmaceutical Classification System hence characterized by high-permeability and low-solubility. Therefore, the dissolution rate is the limiting factor for the gastrointestinal absorption that contributes to the low bioavailability. Consequently, the therapeutic dose of the praziquantel must be high and big tablets and capsules are required, which are difficult to swallow, especially for pediatric and elderly patients. Mixtures of praziquantel and calcium carbonate using solid-solid physical mixtures and solid dispersions were prepared and characterized using several techniques (X-ray diffraction differential scanning calorimetry, thermogravimetric analysis, scanning electron microscopy, laser diffraction, Fourier transform infrared and Raman spectroscopies). Solubility of these formulations evidenced that the solubility of praziquantel-calcium carbonate interaction product increased in physiological media. In vitro dissolution tests showed that the interaction product increased the dissolution rate of the drug in acidic medium. Theoretical models were studied to understand this experimental behavior. Cytotoxicity and cell cycle studies were performed, showing that praziquantel-calcium carbonate physical mixture and interaction product were biocompatible with the HTC116 cells, because it did not produce a decrease in cell viability or alterations in the cell cycle.We also acknowledge for financial support the MINECO, for projects FIS2016-77692-C2-2-P and CGL2016-80833-R, and the Andalusian government, for project RNM1897

What do TSECs provide in the menopausal hormone therapy?

Tissue-selective estrogen complex (TSEC) is projected as a progestogen-free option for the treatment of estrogen deficiency symptoms in postmenopausal, non-hysterectomized women. TSEC combines the benefits of estrogen with a selective estrogen receptor modulator (SERM), in this case bazedoxifene acetate (BZA), which has an antagonistic effect on the endometrium, thus avoiding the use of progestins. The authorized TSEC combination (conjugated estrogens [CE] 0.45mg/BZA 20mg) for the alleviation of vasomotor symptoms has been demonstrated in randomized clinical trials compared with placebo or menopausal hormone therapy (MHT). In addition, TSEC has shown improvements in quality of life and vaginal atrophy. In respect to MHT using progestins, the benefits of TSEC are found mainly in the bleeding pattern, amenorrhea rate, and reduction in mammary repercussion (i.e., breast tenderness and radiological density). The objective of this guide will be to analyze the efficacy and safety of TSEC consisting of CE/BZA in postmenopausal women