Search results for: adverse drug reaction reporting systems

Authors: Ibrahim M. Labouta, Marwa H. El-Wakil, Hayam M. Ashour, Ahmed M. Hassan, Manal N. Saudi

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The receptor tyrosine kinase c-Met is an attractive target for therapeutic treatment of cancers nowadays. Among the wide variety of heterocycles that have been explored for developing c-Met kinase inhibitors, the 1,2,4-triazines have been rarely investigated, although they are well known in the literature to possess antitumor activities. Herein we describe the design and synthesis of a novel series of 1,2,4-triazine derivatives possessing N-acylarylhydrazone moiety and another series combining the 1,2,4-triazine scaffold to the well-known anticancer drug 6-MP in order to explore their “double-drug” effect. The synthesized compounds were evaluated for their in vitro antitumor activity against three c-Met addicted cancer cell lines (A549, HT-29 and MKN-45). Most compounds showed moderate to excellent antiproliferative activity and four compounds showed potent inhibitory activity more than the reference drug Foretinib against one or more cancer cell lines. The obtained results revealed that the potent compounds are highly selective to A549 (lung adenocarcinoma) cancer cell line. The c-Met kinase inhibitory activity of the potent derivatives is still under investigation. The present study clearly demonstrates that the 1,2,4-triazine core ring exhibits promising antitumor activity with potential c-Met kinase inhibitory activity.

Keywords: 1, 2, 4-triazine, antitumor, c-Met inhibitor, double-drug

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Authors: Harish K. Chandrawanshi, Mithun S. Rajput, Neelima Choure, Purnima Dey Sarkar, Shailesh Jain

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The present research study aimed to fabricate and evaluate biodegradable nanoparticles of aromatase inhibitor letrozole, intended for breast cancer therapy. Letrozole loaded poly(D,L-lactide-co-glycolide acid) nanoparticles were prepared by solvent evaporation method using dichlorometane as solvent (oil phase) and polyvinyl alcohol (PVA) as aqueous phase. Prepared nanoparticles were characterized by particle size, infrared spectra, drug loading efficiency, drug entrapment efficiency and in vitro release and also evaluated for in vivo anticancer activity. The high speed homogenizer was used to produce stable nanoparticles of mean size range 198.35 ± 0.04 nm with high entrapment efficiency (69.86 ± 2.78%). Percentage of drug and homogenization speed significantly influenced the particle size, entrapment efficiency and release (p<0.05). The nanoparticles show significant in vivo anticancer activity against Ehrlich ascites carcinoma in mice. The significant system sustained the release of letrozole drug effectively and further investigation could exhibit its potential usefulness in breast cancer therapy.

Keywords: breast cancer/therapy, letrozole, nanoparticles, PLGA

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Authors: Choupani Andisheh, Temucin Elif Sevval, Bediz Bekir

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Due to their various advantages compared to many other drug delivery systems such as hypodermic injections and oral medications, microneedle arrays (MNAs) are a promising drug delivery system. To achieve enhanced performance of the MN, it is crucial to develop numerical models, optimization methods, and simulations. Accordingly, in this work, the optimized design of dissolvable MNAs, as well as their manufacturing, is investigated. For this purpose, a mechanical model of a single MN, having the geometry of an obelisk, is developed using commercial finite element software. The model considers the condition in which the MN is under pressure at the tip caused by the reaction force when penetrating the skin. Then, a multi-objective optimization based on non-dominated sorting genetic algorithm II (NSGA-II) is performed to obtain geometrical properties such as needle width, tip (apex) angle, and base fillet radius. The objective of the optimization study is to reach a painless and effortless penetration into the skin along with minimizing its mechanical failures caused by the maximum stress occurring throughout the structure. Based on the obtained optimal design parameters, master (male) molds are then fabricated from PMMA using a mechanical micromachining process. This fabrication method is selected mainly due to the geometry capability, production speed, production cost, and the variety of materials that can be used. Then to remove any chip residues, the master molds are cleaned using ultrasonic cleaning. These fabricated master molds can then be used repeatedly to fabricate Polydimethylsiloxane (PDMS) production (female) molds through a micro-molding approach. Finally, Polyvinylpyrrolidone (PVP) as a dissolvable polymer is cast into the production molds under vacuum to produce the dissolvable MNAs. This fabrication methodology can also be used to fabricate MNAs that include bioactive cargo. To characterize and demonstrate the performance of the fabricated needles, (i) scanning electron microscope images are taken to show the accuracy of the fabricated geometries, and (ii) in-vitro piercing tests are performed on artificial skin. It is shown that optimized MN geometries can be precisely fabricated using the presented fabrication methodology and the fabricated MNAs effectively pierce the skin without failure.

Keywords: microneedle, microneedle array fabrication, micro-manufacturing structural optimization, finite element analysis

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Authors: Siphesihle Hlongwane

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Background: Globally, alcohol consumption, smoking, and the use of illicit drugs kill more than 11.8 million people each year. In sub-Saharan Africa, substance abuse is responsible for more than 6.4% of all deaths recorded and about 4.7% of all Disability Adjusted Life Years (DALYs), with numbers still expected to grow if no drastic measures are taken to curb and address drug use. In a setting where substance use is rife, understanding contextual factors that influence an individual’s perceived eligibility to seek rehabilitation is paramount. Using the candidacy framework, we unpack how situational factors influence an individual’s perceived eligibility for healthcare uptake in adolescents and youth with substance use disorder (SUD). Methods: The candidacy framework is concerned with how people consider their eligibility for accessing a health service. The study collected and analyzed primary qualitative data to answer the research question. Data were collected between January and July 2022 on participants aged between 18 and 35 for drug users and 18 to 60 for family members. Participants include 20 previous and current drug users and 20 family members that experience the effects of addiction. A pre-drafted semi-structured interview guide was administered to a conveniently sampled population supplemented with a referral sampling method. Data were thematically analyzed using the NVivo 12pro software to manage the data. Findings: Our findings show that people with substance use disorders are aware of their drug use habits and acknowledge their candidacy for health services. Candidacy for health services is also acknowledged by those around them, such as family members and peers, and as such, information on the navigation of health services for drug users is shared by those who have attended health services, those affected by drug use, and this includes health service research by family members to identify accessible health services. While participants reported willingness to quit drug use if assistance is provided, the permeability of health care services is hindered by both individual determinations to quit drug use from long-time use and the availability of health services for drug users, such as rehabilitation centers. Our findings also show that drug users are conscious and can articulate their ailments; however, the hunt for the next dose of drugs and long waiting cues for health service acquisition overshadows their claim to health services. Participants reported a mixture of treatments prescribed, with some more gruesome than others prescribed, thus serving as both a facilitator and barrier for health service uptake. Despite some unorthodox forms of treatments prescribed in health care, the majority of those who enter treatment complete the process of treatment, although some are met with setbacks and sometimes relapse after treatment has finished. Conclusion: Drug users are able to ascertain their candidacy for health services; however, individual and environmental characteristics relating to drug use hinder the use of health services. Drug use interventions need to entice health service uptake as a way to improve candidacy for health use.

Keywords: substance use disorder, rehabilitation, drug use, relapse, South Africa, candidacy framework

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Authors: Wanwimon Mekwimon

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Drug addiction is a serious problem in Thailand which has occurred continuously and repeatedly and enormously impacting health and economy of drug users. The indigenous wisdom and folk medicine is an attractive alternative choice, especially in detoxification and rehabilitation period. There are two objectives: First is to study about rehabilitation process and the curing for drug eaters and 2nd is to investigate the effectiveness of the curing and rehabilitation process by indigenous wisdom at Tamkrabok monastery, Pra-Puttabat district, Saraburi province. The main informants are 10 curers, 15 patients and 17 after-1-year rehabilitators. In the process, the semi-structured questionnaire is administered, the data are analyzed and proved by triangulation. The curing and rehabilitation process which use herbal remedies has a period of 15 days (5 days for detoxification and 10 days for recovery period) and the occupational training and self-consciousness awakening were delivered. The follow-up process includes twice-a-month recall for 6 months, follow-up letters and in depth interview with their families. The outcome of 1 year post-treatment was 94% (16 from 17). There are many reasons for not relapsing: the recovering patients have drawn on their inner strength, self-awareness and coping skill as well as their family and social support while rehabilitation process which includes difficulties in contacting with family members. They can void themselves from high risk situations to relapse. Recommendations: The follow-up system should be improved for continuous quality improvement, there should be the qualification standard for herbal remedies and the comparison among rehabilitation process of Tamkrabok and another methods are to be guideline for the further development.

Keywords: rehabilitation, drug addiction, Thai indigenous knowledge, herbal remedies

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Authors: Adrien Cornille, Marine Blain, Bernard Boutevin, Sylvain Caillol

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Generally, linear polyurethanes (PUs) are obtained by the reaction between an oligomeric diol, a short diol as chain extender and a diisocyanate. However the use of diisocyanate should be avoided since they are generally very harmful for human health. Therefore the synthesis of NIPUs (non isocyanate PUs) from step growth polymerization of dicyclocarbonates and diamines should be favoured. This method is particularly interesting since no hazardous isocyanates are used. Thus, this reaction, extensively studied by Endo et al. is currently gaining a lot of attention as a substitution route for the synthesis of NIPUs, both from industrial and academic community. However, the reactivity of reaction between amine and cyclic carbonate is a major scientific issue, since cyclic carbonates are poorly reactive. Thus, our team developed several synthetic ways for the synthesis of various di-cyclic carbonates based on C5-, C6- and dithio- cyclic carbonates, from different biobased raw materials (glycerin isosorbide, vegetable oils…). These monomers were used to synthesize NIPUs with various mechanical and thermal properties for various applications. We studied the reactivity of reaction with various catalysts and find optimized conditions for room temperature reaction. We also studied the radical copolymerization of cyclic carbonate monomers in styrene-acrylate copolymers for coating applications. We also succeeded in the elaboration of biobased NIPU flexible foams. To the best of our knowledge, there is no report in literature on the preparation of non-isocyanate polyurethane foams.

Keywords: foam, nonisocyanate polyurethane, cyclic carbonate, blowing agent, scanning electron microscopy

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Authors: Tanakrit Doltanakarn

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Introduction: These days, cannabis is being accepted in many countries due to the fact that cannabis could be use in medical. The medical cannabis is used to treat and reduce the pain many diseases. For example, neuropathic pain, Parkinson, autism disorders, cancer pain reduce the adverse effect of chemotherapy, diabetes, and migraine. Active ingredients in cannabis that modulate patients' perceptions of their conditions include Δ9‐tetrahydrocannabinol (THC), cannabidiol (CBD), flavonoids, and terpenes. However, there is an adverse effect of cannabis, cardiovascular effects, psychosis, schizophrenia, mood disorder, and cognitive alternation. These effects are from the THC and CBD ingredients in the cannabis. The metabolize processes of delta-9 THC to 11-OH-delta 9 -THC (inactive form), THC were cause of adverse effects. Interestingly, the distributions of CYP2C9 gene (CYP2C9*2 and CYP2C9*3, poor metabolizer) that might affect incidences of adverse effects in patients who treated with medical cannabis. Objective: The aim of this study we want to investigate the association between genetic polymorphism of CYP2C9 frequency and Thai patients who treated with medical cannabis. Materials and Methods:We recruited sixty-five unrelated Thai patients from the College of Pharmacy, Rangsit University. DNA were extracted using Genomic DNA Mini Kit. Genotyping of CYP2C9*2 (430C>T, rs1799853) and CYP2C9*3 (1075A>C, rs1057910) were genotyped by the TaqMan Real-time PCR assay. Results: Among these 31 medicals cannabis-induced ADRs patients, they were diagnosed with 22 (33.85%) tachycardia and 3 (4.62%) arrhythmia. There were 34 (52.31%) medical cannabis-tolerant controls who were included in this study.40 (61.53%) Thai patients were female, and 25 (38.46%) were male, with median age of 57 (range 27 – 87) years. In this study, we found none of the medical cannabis-induced ADRs carried CYP2C9*2 variant along with medical cannabis-tolerant control group. CYP2C9*3 variant (intermediate metabolizer, IM) was found just only one of thirty-one (3.23%) in the medical cannabis-induced ADRs and two of thirty-fourth (5.88%) in the tolerant controls. Conclusions: Thus, the distribution of CYP2C9 alleles offer a comprehensive view of pharmacogenomics marker in Thai population that could be used as a reference for worldwide to investigate the pharmacogenomics application.

Keywords: medical cannabis, adverse effect, CYP2C9, thai patients

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Authors: Yongde Xia, Laicong Deng, Zhuxian Yang

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Developing cost-effective electrocatalysts for oxygen reduction reaction (ORR), oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) is vital in energy conversion and storage applications. Herein, we report a simple method for the synthesis of graphene-reinforced cobalt sulfide/carbon nanocomposites and the evaluation of their electrocatalytic performance for typical electrocatalytic reactions. Nanocomposites of cobalt sulfide embedded in N, S co-doped porous carbon and graphene (CoS@C/Graphene) were generated via simultaneous sulfurization and carbonization of one-pot synthesized graphite oxide-ZIF-67 precursors. The obtained CoS@C/Graphene nanocomposite was characterized by X-ray diffraction, Raman spectroscopy, Thermogravimetric analysis-Mass spectroscopy, Scanning electronic microscopy, Transmission electronic microscopy, X-ray photoelectron spectroscopy and gas sorption. It was found that cobalt sulfide nanoparticles were homogenously dispersed in the in-situ formed N, S co-doped porous carbon/Graphene matrix. The CoS@C/10Graphene composite not only shows excellent electrocatalytic activity toward ORR with high onset potential of 0.89 V, four-electron pathway and superior durability of maintaining 98% current after continuously running for around 5 hours, but also exhibits good performance for OER and HER, due to the improved electrical conductivity, increased catalytic active sites and connectivity between the electrocatalytic active cobalt sulfide and the carbon matrix. This work offers a new approach for the development of novel multifunctional nanocomposites for the next generation of energy conversion and storage applications.

Keywords: MOF derivative, graphene, electrocatalyst, oxygen reduction reaction, oxygen evolution reaction, hydrogen evolution reaction

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Authors: Naima Bouslah, Leila Bounabi, Farid Ouazib, Nabila Haddadine

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Conventional release dosage forms are known to provide an immediate release of the drug. Controlling the rate of drug release from polymeric matrices is very important for a number of applications, particularly in the pharmaceutical area. Hydrogels are polymers in three-dimensional network arrangement, which can absorb and retain large amounts of water without dissolution. They have been frequently used to develop controlled released formulations for oral administration because they can extend the duration of drug release and thus reduce dose to be administrated improving patient compliance. Tramadol is an opioid pain medication used to treat moderate to moderately severe pain. When taken as an immediate-release oral formulation, the onset of pain relief usually occurs within about an hour. In the present work, we synthesized pH-responsive hydrogels of (hydroxyl ethyl methacrylate-co-acrylic acid), (HEMA-AA) for control drug delivery of tramadol in the gastro-intestinal tractus. The hydrogels with different acrylic acid content, were synthesized by free radical polymerization and characterized by FTIR spectroscopy, X ray diffraction analysis (XRD), differential scanning calorimetry (DSC) and thermo gravimetric analysis (TGA). FTIR spectroscopy has shown specific hydrogen bonding interactions between the carbonyl groups of the hydrogels and hydroxyl groups of tramadol. Both the XRD and DSC studies revealed that the introduction of tramadol in the hydrogel network induced the amorphization of the drug. The swelling behaviour, absorptive kinetics and the release kinetics of tramadol in simulated gastric fluid (pH 1.2) and in simulated intestinal fluid (pH 7.4) were also investigated. The hydrogels exhibited pH-responsive behavior in the swelling study. The (HEMA-AA) hydrogel swelling was much higher in pH =7.4 medium. The tramadol release was significantly increased when pH of the medium was changed from simulated gastric fluid (pH 1.2) to simulated intestinal fluid (pH 7.4). Using suitable mathematical models, the apparent diffusional coefficients and the corresponding kinetic parameters have been calculated.

Keywords: biopolymres, drug delivery, hydrogels, tramadol

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Authors: Sutapa Mondal Roy, Suban K. Sahoo

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The primary aim of this work is to synthesis silver nanoparticles (AgNPs) through environmentally benign routes to avoid any chemical toxicity related undesired side effects. The nanoparticles were stabilized with drug ciprofloxacin (Cp) and were studied for their effectiveness as drug delivery agent. Targeted drug delivery improves the therapeutic potential of drugs at the diseased site as well as lowers the overall dose and undesired side effects. The small size of nanoparticles greatly facilitates the transport of active agents (drugs) across biological membranes and allows them to pass through the smallest capillaries in the body that are 5-6 μm in diameter, and can minimize possible undesired side effects. AgNPs are non-toxic, inert, stable, and has a high binding capacity and thus can be considered as biomaterials. AgNPs were synthesized from the nutrient broth supernatant after the culture of environment-friendly bacteria Bacillus subtilis. The AgNPs were found to show the surface plasmon resonance (SPR) band at 425 nm. The Cp capped Ag nanoparticles formation was complete within 30 minutes, which was confirmed from absorbance spectroscopy. Physico-chemical nature of the AgNPs-Cp system was confirmed by Dynamic Light Scattering (DLS), Transmission Electron Microscopy (TEM) etc. The AgNPs-Cp system size was found to be in the range of 30-40 nm. To monitor the kinetics of drug release from the surface of nanoparticles, the release of Cp was carried out by careful dialysis keeping AgNPs-Cp system inside the dialysis bag at pH 7.4 over time. The drug release was almost complete after 30 hrs. During the drug delivery process, to understand the AgNPs-Cp system in a better way, the sincere theoretical investigation is been performed employing Density Functional Theory. Electronic charge transfer, electron density, binding energy as well as thermodynamic properties like enthalpy, entropy, Gibbs free energy etc. has been predicted. The electronic and thermodynamic properties, governed by the AgNPs-Cp interactions, indicate that the formation of AgNPs-Cp system is exothermic i.e. thermodynamically favorable process. The binding energy and charge transfer analysis implies the optimum stability of the AgNPs-Cp system. Thus, the synthesized Cp-Ag nanoparticles can be effectively used for biological purposes due to its environmentally benign routes of synthesis procedures, which is clean, biocompatible, non-toxic, safe, cost-effective, sustainable and eco-friendly. The Cp-AgNPs as biomaterials can be successfully used for drug delivery procedures due to slow release of drug from nanoparticles over a considerable period of time. The kinetics of the drug release show that this drug-nanoparticle assembly can be effectively used as potential tools for therapeutic applications. The ease of synthetic procedure, lack of possible chemical toxicity and their biological activity along with excellent application as drug delivery agent will open up vista of using nanoparticles as effective and successful drug delivery agent to be used in modern days.

Keywords: silver nanoparticles, ciprofloxacin, density functional theory, drug delivery

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Authors: Tanvir Ahmed, Thanh N. Long, Phan T. Huong, Donald E. Stewart

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This paper presents views on condom use and the contexts of safe and unsafe sexual practices with different sexual partners and their relationships among Injecting Drug Users (IDUs) in Hai Phong, Vietnam. Fifteen IDUs participated and two local interviewers conducted qualitative semi-structured face-to-face interviews in September-October, 2012 in Vietnamese language. Data were analyzed thematically. Non-protective condom attitudes include negotiate or convince Female Sex Workers (FSW); not realizing risk, importance or necessity; partner doesn’t like, and having extra money/drug from clients. On the other hand, self-awareness, family-consciousness, suspicion of STI presence, fear of getting HIV, and client negotiation sometimes resulted in a safe-sex practice. A thematic diagram was developed to present the relationship (strong/weak) between condom attitude and sexual practice (safe/unsafe) by partner types. The experiences and views reflected in the qualitative information emphasize the heightened need for safe-sex education especially among young IDUs (male/female) highlighting sexual transmission risk.

Keywords: AIDS, HIV, injecting drug user, risk behaviors, Vietnam

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Authors: Peramachi Sathiyamoorthy, Jacop Gopas, Avi Golan Goldhirsh

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Corchorus olitorius is a leafy vegetable and an industrial crop. The herb has antioxidant, anti inflammatory, and anti-cancer properties. To assay the pharmaceutical properties, aqueous extracts of leaves and seeds from C. olitorius were tested against drug resistant melanoma cell line. The test showed LC50 of the extract was 0.08µg/ml. Aqueous seed extract exhibited higher melanoma inhibiting activity than leaf extract. Dialysis of seed extract showed that the active compound is less than 12 KDa. The compound with <3 KDa MW separated by microconcentration of seed extract showed 70.5 % inhibition of melanoma cell growth. Among the two fractions obtained by Gel filtration with G10 column, the first fraction at 1:2000 dilutions exhibited 100% inhibition of melanoma growth. The compound with Rf value 0.86 (MA4) isolated by TLC separation showed about 98% cytotoxicity against melanoma at 1: 1000 dilutions. Furthermore, HPLC separation of MA4 compound with Superdex 75 column resulted in 4 compounds. Out of 4, one compound showed melanoma inhibition. The active compound is identified by reagent methods as Strophanthidin. Further toxicological and clinical studies will lead to the development of a potential drug to treat drug resistant melanoma.

Keywords: corchorus olitorius, melanoma, drug development, strophanthidin

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Authors: Vishal D. Bharud, B. J. Patil, S. S. Dahiwale, V. N. Bhoraskar, S. D. Dhole

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Photon induced average reaction cross section of ¹¹¹Cd (γ, γ`) ¹¹¹ᵐCd reaction was experimentally determined for the bremsstrahlung energy spectrum of 6 MeV by utilizing the activation and offline γ-ray spectrometric techniques. The 6 MeV electron accelerator Racetrack Microtron of Savitribai Phule Pune University, Pune was used for the experimental work. The bremsstrahlung spectrum generated by bombarding 6 MeV electrons on lead target was theoretically estimated by FLUKA code. Bremsstrahlung radiation can have energies exceeding the threshold of the particle emission, which is normally above 6 MeV. Photons of energies below the particle emission threshold undergo absorption into discrete energy levels, with possibility of exciting nuclei to excited state including metastable state. The ¹¹¹Cd (γ, γ`) ¹¹¹ᵐCd reaction cross sections were calculated at different energies of bombarding Photon by using the TALYS 1.8 computer code with a default parameter. The focus of the present work was to study the (γ,γ’) reaction for exciting ¹¹¹Cd nuclei to metastable states which have threshold energy below 3 MeV. The flux weighted average cross section was obtained from the theoretical values of TALYS 1.8 and TENDL 2017 and is found to be in good agreement with the present experimental cross section.

Keywords: bremsstrahlung, cross section, FLUKA, TALYS-1.8

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Authors: Grant Bifolchi

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As global environmental problems continue to have highly adverse effects, finding long-term, sustainable solutions to combat ecological distress are of growing paramount concern. Ghost Gear—also known as abandoned, lost or otherwise discarded fishing gear (ALDFG) and derelict fishing gear (DFG)—represents one of the greatest threats to the world’s oceans, posing a significant hazard to human health, livelihoods, and global food security. In fact, according to the UN Food and Agriculture Organization (FAO), abandoned, lost and discarded fishing gear represents approximately 10% of marine debris by volume. Around the world, many governments, governmental and non-profit organizations are doing their best to manage the reporting and retrieval of nets, lines, ropes, traps, floats and more from their respective bodies of water. However, these organizations’ ability to effectively manage files and documents about the environmental problem further complicates matters. In Ghost Gear monitoring and management, organizations face additional complexities. Whether it’s data ingest, industry regulations and standards, garnering actionable insights into the location, security, and management of data, or the application of enforcement due to disparate data—all of these factors are placing massive strains on organizations struggling to save the planet from the dangers of Ghost Gear. In this 90-minute educational session, globally recognized Ghost Gear technology expert Grant Bifolchi CET, BBA, Bcom, will provide real-world insight into how governments currently manage Ghost Gear and the technology that can accelerate success in combatting ALDFG and DFG. In this session, attendees will learn how to: • Identify specific technologies to solve the ingest and management of Ghost Gear data categories, including type, geo-location, size, ownership, regional assignment, collection and disposal. • Provide enhanced access to authorities, fisheries, independent fishing vessels, individuals, etc., while securely controlling confidential and privileged data to globally recognized standards. • Create and maintain processing accuracy to effectively track ALDFG/DFG reporting progress—including acknowledging receipt of the report and sharing it with all pertinent stakeholders to ensure approvals are secured. • Enable and utilize Business Intelligence (BI) and Analytics to store and analyze data to optimize organizational performance, maintain anytime-visibility of report status, user accountability, scheduling, management, and foster governmental transparency. • Maintain Compliance Reporting through highly defined, detailed and automated reports—enabling all stakeholders to share critical insights with internal colleagues, regulatory agencies, and national and international partners.

Keywords: ghost gear, ALDFG, DFG, abandoned, lost or otherwise discarded fishing gear, data, technology

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Authors: Calvin A. Omolo, Rahul S. Kalhapure, Mahantesh Jadhav, Sanjeev Rambharose, Chunderika Mocktar, Thirumala Govender

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Treatment of infections is compromised by limitations of conventional dosage forms and drug resistance. Nanocarrier system is a strategy to overcome these challenges and improve therapy. Thus, the development of novel materials for drug delivery via nanocarriers is essential. The aim of the study was to synthesize a multi-arm polymer (6-mPEPEA) for enhanced activity of vancomycin (VM) against susceptible and resistant Staphylococcus aureus (MRSA). The synthesis steps of the star polymer followed reported procedures. The synthesized 6-mPEPEA was characterized by FTIR, ¹H and ¹³CNMR and MTT assays. VM loaded micelles were prepared from 6-mPEPEA and characterized for size, polydispersity index (PI) and surface charge (ZP) (Dynamic Light Scattering), morphology by TEM, drug loading (UV Spectrophotometry), drug release (dialysis bag), in vitro and in vivo efficacy against sensitive and resistant S. aureus. 6-mPEPEA was synthesized, and its structure was confirmed. MTT assays confirmed its nontoxic nature with a high cell viability (77%-85%). Unimolecular spherical micelles were prepared. Size, PI, and ZP was 52.48 ± 2.6 nm, 0.103 ± 0.047, -7.3 ± 1.3 mV, respectively and drug loading was 62.24 ± 3.8%. There was a 91% drug release from VCM-6-mPEPEA after 72 hours. In vitro antibacterial test revealed that VM-6-mPEPEA had 8 and 16-fold greater activity against S. aureus and MRSA when compared to bare VM. Further investigations using flow cytometry showed that VM-6-mPEPEA had 99.5% killing rate of MRSA at the MIC concentration. In vivo antibacterial activity revealed that treatment with VM-6-mPEPEA had a 190 and a 15-fold reduction in the MRSA load in untreated and VM treated respectively. These findings confirmed the potential of 6-mPEPEA as a promising bio-degradable nanocarrier for antibiotic delivery to improve treatment of bacterial infections.

Keywords: biosafe, MRSA, nanocarrier, resistance, unimolecular-micelles

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Authors: Aleksandra Łochowicz, Daria Świętochowska, Loredano Pollegioni, Nazim Ocal, Franck Charmantray, Laurence Hecquet, Katarzyna Szymańska

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Multienzymatic cascade reactions are nowadays widely used in pharmaceutical, chemical and cosmetics industries to produce high valuable compounds. They can be carried out in two ways, step by step and one-pot. If two or more enzymes are in the same reaction vessel is necessary to work out the compromise to run the reaction in optimal conditions for each enzyme. So far most of the reports of multienzymatic cascades concern on usage of free enzymes. Unfortunately using free enzymes as catalysts of reactions accomplish high cost. What is more, free enzymes are soluble in solvents which makes reuse impossible. To overcome this obstacle enzymes can be immobilized what provides heterogeneity of biocatalyst that enables reuse and easy separation of the enzyme from solvents and reaction products. Usually, immobilization increase also the thermal and operational stability of enzyme. The advantages of using immobilized multienzymes are enhanced enzyme stability, improved cascade enzymatic activity via substrate channeling, and ease of recovery for reuse. The one-pot immobilized multienzymatic cascade can be carried out in mixed or coimmobilized type. When biocatalysts are coimmobilized on the same carrier the are in close contact to each other which increase the reaction rate and catalytic efficiency, and eliminate the lag time. However, in this type providing the optimal conditions both in the process of immobilization and cascade reaction for each enzyme is complicated. Herein, we examined immobilization of 3 enzymes: D-amino acid oxidase from Rhodotorula gracilis, commercially available catalase and transketolase from Geobacillus stearothermophilus. As a support we used silica monoliths with hierarchical structure of pores. Then we checked their stability and reusability in one-pot cascade of L-erythrulose and hydroxypuryvate acid synthesis.

Keywords: biocatalysts, enzyme immobilization, multienzymatic reaction, silica carriers

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Authors: Olukayode Bamgbose, Feyisola Agboola, Adewale M. Taiwo, Olanrewaju Olujimi Oluwole Terebo, Azeez Soyingbe, Akeem Bamgbade

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The present study evaluated the contents and health risk assessment of metals determined in milk and milk product samples collected from the Abeokuta market. Forty-five milk and milk product (yoghurt) samples were digested and analysed for selected metals using Atomic Absorption Spectrophotometric method. Health risk assessment was evaluated for hazard quotient (HQ), hazard index (HI), and cancer risk (CR). Data were subjected to descriptive and inferential statistics. The concentrations of Zn, which ranged from 3.24±0.59 to 4.35±0.59 mg/kg, were the highest in the samples. Cr and Cd were measured below the detection limit of the analytical instrument, while the Pb level was higher than the Codex Alimentarius Commission value of 0.02 mg/kg, indicating unsafe for consumption. However, the HQ of Pb and other metals in milk and milk product samples was less than 1.0, thereby establishing no adverse health effects for Pb and other metals. The distribution pattern of metals in milk and milk product samples followed the decreasing order of Zn > Fe > Ni > Co > Cu > Mn > Pb > Cd/Cr. The CR levels of meals were also less than the permissible limit of 1.0 x 10-4, establishing no possible development of cancer. Keywords: adverse effects, cancer, metals, milk, milk product, the permissible limit.

Keywords: adverse effects, cancer, metals, milk, milk product, permissible limit

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Authors: Jigar N. Shah, Hiral J. Shah, Praful D. Bharadia

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The major challenge faced by formulation scientists in transdermal drug delivery system is to overcome the inherent barriers related to skin permeation. The stratum corneum layer of the skin is working as the rate limiting step in transdermal transport and reduce drug permeation through skin. Many approaches have been used to enhance the penetration of drugs through this layer of the skin. The purpose of this study is to investigate the development and evaluation of a combined approach of drug carriers and iontophoresis as a vehicle to improve skin permeation of an analgesic drug. Iontophoresis is a non-invasive technique for transporting charged molecules into and through tissues by a mild electric field. It has been shown to effectively deliver a variety of drugs across the skin to the underlying tissue. In addition to the enhanced continuous transport, iontophoresis allows dose titration by adjusting the electric field, which makes personalized dosing feasible. Drug carrier could modify the physicochemical properties of the encapsulated molecule and offer a means to facilitate the percutaneous delivery of difficult-to-uptake substances. Recently, there are some reports about using liposomes, microemulsions and polymeric nanoparticles as vehicles for iontophoretic drug delivery. Niosomes, the nonionic surfactant-based vesicles that are essentially similar in properties to liposomes have been proposed as an alternative to liposomes. Niosomes are more stable and free from other shortcoming of liposomes. Recently, the transdermal delivery of certain drugs using niosomes has been envisaged and niosomes have proved to be superior transdermal nanocarriers. Proniosomes overcome some of the physical stability related problems of niosomes. The proniosomal structure was liquid crystalline-compact niosomes hybrid which could be converted into niosomes upon hydration. The combined use of drug carriers and iontophoresis could offer many additional benefits. The system was evaluated for Encapsulation Efficiency, vesicle size, zeta potential, Transmission Electron Microscopy (TEM), DSC, in-vitro release, ex-vivo permeation across skin and rate of hydration. The use of proniosomal gel as a vehicle for the transdermal iontophoretic delivery was evaluated in-vitro. The characteristics of the applied electric current, such as density, type, frequency, and on/off interval ratio were observed. The study confirms the synergistic effect of proniosomes and iontophoresis in improving the transdermal permeation profile of selected analgesic drug. It is concluded that proniosomal gel can be used as a vehicle for transdermal iontophoretic drug delivery under suitable electric conditions.

Keywords: iontophoresis, niosomes, permeation enhancement, transdermal delivery

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Authors: Asma Ansari, Afsheen Aman, Shah Ali Ul Qader

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In the past few years, numerous concerns have been raised against increased bacterial resistance towards effective drugs and become a debated issue all over the world. With the emergence of drug resistant pathogens, the interaction of natural antimicrobial compounds and antibacterial nanoparticles has emerged as a potential candidate for combating infectious diseases. Microbial diversity in the biome provides an opportunity to screen new species which are capable of producing large number of antimicrobial compounds. Among these antimicrobial compounds, bacteriocins are highly specific and efficient antagonists. A combination of bacteriocin along with nanoparticles could prove to be more potent due to broadened antibacterial spectrum with possibly lower doses. In the current study, silver nanoparticles were synthesized through biological reduction using various isolated bacterial, fungal and yeast strains. Spectroscopy and scanning electron microscopy (SEM) was performed for the confirmation of nanoparticles. Bacteriocin was characterized and purified to homogeneity through gel permeation chromatography. The estimated molecular weight of bacteriocin was 10 kDa. Amino acid analysis and N-terminal sequencing revealed the novelty of the protein. Then antibacterial potential of silver nanoparticles and broad inhibitory spectrum bacteriocin was determined through agar well diffusion assay. These synthesized bacteriocin-Nanoparticles exhibit a good potential for clinical applications as compared to bacteriocin alone. This combination of bacteriocin with nanoparticles will be used as a new sort of biocide in the field of nano-proteomics. The advancement of nanoparticles-mediated drug delivery system will open a new age for rapid eradication of pathogens from biological systems.

Keywords: BAC-IB17, multidrug resistance, purification, silver nanoparticles

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Authors: Takeyuki Suzuki, Ismiyarto, Da-Yang Zhou, Kaori Asano, Hiroaki Sasai

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The development of catalytic asymmetric reaction is important for the synthesis of natural products. To construct the multiple stereogenic centers, the desymmetrization of meso compounds is powerful strategy for the synthesis of chiral molecules. Oxidative desymmetrization of meso diols using chiral iridium catalyst provides a chiral hydroxyl ketone. The reaction is practical and an environmentally benign method which does not require the use of stoichiometric amount of heavy metals. This time we report here catalytic asymmetric synthesis of catalponol based on tandem coupling of meso-diols and an aldehyde. The tandem reaction includes oxidative desymmetrization of meso-diols, aldol condensation with an aldehyde. The reaction of meso-diol, benzaldehyde in the presence of a catalytic amount of chiral Ir complex and CsOH in tetrahydrofuran afforded the desired benzylidene ketone in 82% yield with 96% ee (enantiomeric excess). Next, we applied this benzylidene ketone derivative to the synthesis of catalponol. The corresponding benzylidene ketone was obtained in 87% yield with 99% ee. Finally, catalponol was synthesized by the regio- and stereo-selective reduction of dienone moiety in good yield.

Keywords: catalponol, desymmetrization, iridium, oxidation

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Authors: Wajid Rehman, Sirajul Haq, Bakhtiar Muhammad, Syed Fahad Hassan, Amin Badshah, Muhammad Waseem, Fazal Rahim, Obaid-Ur-Rahman Abid, Farzana Latif Ansari, Umer Rashid

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Five novel triorganotin (IV) compounds have been synthesized and characterized. The tin atom is penta-coordinated to assume trigonal-bipyramidal geometry. Using in silico derived parameters; the objective of our study is to design and synthesize promiscuous antibacterials potent enough to combat resistance. Among various synthesized organotin (IV) complexes, compound 5 was found as potent antibacterial agent against various bacterial strains. Further lead optimization of drug-like properties was evaluated through in silico predictions. Data mining and computational analysis were utilized to derive compound promiscuity phenomenon to avoid drug attrition rate in designing antibacterials. Xanthine oxidase and human glucose- 6-phosphatase were found as only true positive off-target hits by ChEMBL database and others utilizing similarity ensemble approach. Propensity towards a-3 receptor, human macrophage migration factor and thiazolidinedione were found as false positive off targets with E-value 1/4> 10^-4 for compound 1, 3, and 4. Further, displaying positive drug-drug interaction of compound 1 as uricosuric was validated by all databases and docked protein targets with sequence similarity and compositional matrix alignment via BLAST software. Promiscuity of the compound 5 was further confirmed by in silico binding to different antibacterial targets.

Keywords: antibacterial activity, drug promiscuity, ADMET prediction, metallo-pharmaceutical, antimicrobial resistance

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Authors: Hossein Anaraki-Ardakani, Tayebe Heidari-Rakati

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An environmentally benign protocol for the one-pot, three-component synthesis of Triazolo[1,2-a]indazole-1,3,8-trione derivatives by condensation of dimedone, urazole and aromatic aldehydes catalyzed by HClO4/SiO2 NPS as an ecofriendly catalyst with high catalytic activity and reusability at 100 ºC under solvent-free conditions is reported. The reaction proceeds to completion within 20-30 min in 77-86 % yield.

Keywords: one-pot reaction, dimedone, triazoloindazole, urazole

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Authors: Kuheli Chakrabarty, Animesh Ghosh, Atanu Roy, Gourab Kanti Das

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Aldol reaction is an important class of carbon-carbon bond forming reactions. One of the popular ways to impose asymmetry in aldol reaction is the introduction of chiral auxiliary that binds the approaching reactants and create dissymmetry in the reaction environment, which finally evolves to enantiomeric excess in the aldol products. The last decade witnesses the usage of natural amino acids as chiral auxiliary to control the stereoselectivity in various carbon-carbon bond forming processes. In this context, L-proline was found to be an effective organocatalyst in asymmetric aldol additions. In last few decades the use of water as solvent or co-solvent in asymmetric organocatalytic reaction is increased sharply. Simple amino acids like L-proline does not catalyze asymmetric aldol reaction in aqueous medium not only that, In organic solvent medium high catalytic loading (~30 mol%) is required to achieve moderate to high asymmetric induction. In this context, huge efforts have been made to modify L-proline and 4-hydroxy-L-proline to prepare organocatalyst for aqueous medium asymmetric aldol reaction. Here, we report the result of our DFT calculations on asymmetric aldol reaction of benzaldehyde, p-NO2 benzaldehyde and t-butyraldehyde with a number of ketones using L-proline hydrazide as organocatalyst in wet solvent free condition. Gaussian 09 program package and Gauss View program were used for the present work. Geometry optimizations were performed using B3LYP hybrid functional and 6-31G(d,p) basis set. Transition structures were confirmed by hessian calculation and IRC calculation. As the reactions were carried out in solvent free condition, No solvent effect were studied theoretically. Present study has revealed for the first time, the direct involvement of two water molecules in the aldol transition structures. In the TS, the enamine and the aldehyde is connected through hydrogen bonding by the assistance of two intervening water molecules forming a supramolecular network. Formation of this type of supramolecular assembly is possible due to the presence of protonated -NH2 group in the L-proline hydrazide moiety, which is responsible for the favorable entropy contribution to the aldol reaction. It is also revealed from the present study that, water assisted TS is energetically more favorable than the TS without involving any water molecule. It can be concluded from this study that, insertion of polar group capable of hydrogen bond formation in the L-proline skeleton can lead to a favorable aldol reaction with significantly high enantiomeric excess in wet solvent free condition by reducing the activation barrier of this reaction.

Keywords: aldol reaction, DFT, organocatalysis, transition structure

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Authors: Mahera Abdulrahman, Satish Chandrasekhar Nair

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Growing demand for human health research in the United Arab Emirates (UAE) has prompted the need to develop a robust research ethics oversight, particularly given the large unskilled-worker immigrant population and the elderly citizens utilizing health services. Examination of the structure, function, practices and outcomes of the human research ethics committees (HREC) was conducted using two survey instruments, reliable and validated. Results indicate that in the absence of a national ethics regulatory body, the individual emirate’s governed 21 HRECs covering health facilities and academic institutions in the UAE. Among the HRECs, 86% followed International Council for Harmonization-Good Clinical Practice guidelines, 57% have been in operation for more than five years, 81% reviewed proposals within eight weeks, 48% reviewed for clinical and scientific merit apart from ethics, and 43% handled more than 50 research proposals per year. However, researcher recognition, funding transparency, adverse event reporting systems were widespread in less than one-third of all HRECs. Surprisingly, intellectual property right was not included as a research output. Research was incorporated into the vision and mission statements of many (62%) organizations and, mechanisms such as research publications, collaborations, and recognitions were employed as key performance indicators to measure research output. In spite, resources to generate research output such as dedicated budget (19%), support staff (19%) and continuous training and mentoring program for medical residents and HREC members were somehow lacking. HREC structure and operations in the UAE are similar to other regions of the world, resources allocation for efficient, quality monitoring, continuous training, and the creation of a clinical research network are needed to strengthen the clinical research enterprise to scale up for the future. It is anticipated that the results of this study will benefit investigators, regulators, pharmaceutical sponsors and the policy makers in the region.

Keywords: institutional review board, ethics committee, human research ethics, United Arab Emirates (UAE)

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Authors: Parikshit Gogo, N. N. Dutta

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The oxidative enzymes specially laccase (benzenediol: oxygen oxidoreductase, E.C.1.10.3.2) from bacteria, fungi and plants have been playing an important role in green technologies due to their specific advantageous properties. Laccase from different sources and in different forms was used as a biocatalyst in many oxidation and conjugation reactions starting from phenol to hydrocarbons. Tea polyphenols and its derivatives attract the scientific community because of their potential use as antioxidants in food, pharmaceutical and cosmetic industries. Conjugate of polyphenols emerged as a novel materials which shows better stability and antioxidant properties in applied fields. The conjugation reaction of catechin with poly (allylamine) has been studied using free, immobilized and cross-linked enzyme crystals (CLEC) of laccase from Trametes versicolor with particular emphasis on the effect of pertinent variables and kinetic aspects of the reaction. The stability and antioxidant property of the conjugated product was improved as compared to the unconjugated tea polyphenols. The reaction was studied in 11 different solvents in order to deduce the solvent effect through an attempt to correlate the initial reaction rate with solvent properties such as hydrophobicity (logP), water solubility (logSw), electron pair acceptance (ETN) and donation abilities (DNN), polarisibility and dielectric constant which exhibit reasonable correlations. The study revealed, in general that polar solvents favour the initial reaction rate. The kinetics of the conjugation reaction conformed to the so-called Ping-Pong-Bi-Bi mechanism with catechin inhibition. The stability as well as activity of the CLEC was better than the free enzymes and immobilized laccase for practical application. In case of immobilized laccase system marginal diffusional limitation could be inferred from the experimental data. The kinetic parameters estimated by non-linear regression analysis were found to be KmPAA(mM) = 0.75, 1.8967 and Kmcat (mM) = 11.769, 15.1816 for free and immobilized laccase respectively. An attempt has been made to assess the activity of the laccase for the conjugation reaction in relation to other reactions such as dimerisation of ferulic acids and develop a protocol to enhance polyphenol antioxidant activity.

Keywords: laccase, catechin, conjugation reaction, antioxidant properties

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Authors: K. Chethana, A. S. Guru Prasad, S. N. Omkar, B. Vadiraj, S. Asokan

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This paper describes an ab-initio design, development and calibration results of an Optical Sensor Ground Reaction Force Measurement Platform (OSGRFP) for gait and geriatric studies. The developed system employs an array of FBG sensors to measure the respective ground reaction forces from all three axes (X, Y and Z), which are perpendicular to each other. The novelty of this work is two folded. One is in its uniqueness to resolve the tri axial resultant forces during the stance in to the respective pure axis loads and the other is the applicability of inherently advantageous FBG sensors which are most suitable for biomechanical instrumentation. To validate the response of the FBG sensors installed in OSGRFP and to measure the cross sensitivity of the force applied in other directions, load sensors with indicators are used. Further in this work, relevant mathematical formulations are presented for extracting respective ground reaction forces from wavelength shifts/strain of FBG sensors on the OSGRFP. The result of this device has implications in understanding the foot function, identifying issues in gait cycle and measuring discrepancies between left and right foot. The device also provides a method to quantify and compare relative postural stability of different subjects under test, which has implications in post surgical rehabilitation, geriatrics and optimizing training protocols for sports personnel.

Keywords: balance and stability, gait analysis, FBG applications, optical sensor ground reaction force platform

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Authors: Shuo Mu, Guangzhi Jiang, Jinsa Chen

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The analysis of Indel for RNA sequencing of clinical samples is easily affected by sequencing experiment errors and software selection. In order to improve the efficiency and accuracy of analysis, we developed an automatic reporting system for Indel recognition and annotation based on image snapshot of transcriptome reads alignment. This system includes sequence local-assembly and realignment, target point snapshot, and image-based recognition processes. We integrated high-confidence Indel dataset from several known databases as a training set to improve the accuracy of image processing and added a bioinformatical processing module to annotate and filter Indel artifacts. Subsequently, the system will automatically generate data, including data quality levels and images results report. Sanger sequencing verification of the reference Indel mutation of cell line NA12878 showed that the process can achieve 83% sensitivity and 96% specificity. Analysis of the collected clinical samples showed that the interpretation accuracy of the process was equivalent to that of manual inspection, and the processing efficiency showed a significant improvement. This work shows the feasibility of accurate Indel analysis of clinical next-generation sequencing (NGS) transcriptome. This result may be useful for RNA study for clinical samples with microsatellite instability in immunotherapy in the future.

Keywords: automatic reporting, indel, next-generation sequencing, NGS, transcriptome

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Authors: Mohd Asharf Ganie, Aafia Rashid, Mohd Afzal Zargar, Showkat Ali Zargar, Syed Mudasar, Tabasum Parvaiz, Zafar Amin Shah

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Accumulating evidence suggests that Vitamin D deficiency (VDD) might at least contribute to the metabolic co-morbidities in PCOS. Hence, we aimed to study the effect of vitamin D supplementation in co-prescription with insulin sensitizers like metformin and pioglitazone on clinical, hormonal and metabolic parameters in women with PCOS. In this open label randomized, controlled trial a total of 120 women with PCOS diagnosis (AE-PCOS 2009 Criteria) were assigned to four treatment groups (n= 30 in each): group I (metformin 1 gm/day in combination with cholecalciferol 4000 IU/day), group II (pioglitazone 30 mg/day in combination with cholecalciferol 4000 IU/day), group III (metformin 1 gm /day) and group IV (pioglitazone 30 mg/day). Vitamin D supplementation was given as 60,000 units every two weeks for 24 weeks. All the subjects were routinely evaluated for clinical, biochemical, hormonal and insulin sensitivity parameters in addition to various safety parameters especially serum calcium levels at baseline and after 24 weeks of the treatment. Our results indicate that 95.5% of PCOS women were vitamin D deficient at baseline. Serum 25 (OH) D levels increased significantly (p < 0.001) in groups I and II without any adverse effects after 24 weeks of oral administration of 4000 IU cholecalciferol daily. However, serum 25 (OH) D levels remained unchanged in group III and IV. By six months, number of menstrual cycles per year increased whereas Ferriman-Gallwey score, serum total testosterone and HOMA-IR decreased significantly (P < 0.001) in the treatment groups supplemented with cholecalciferol as compared to those treated either drug alone. No significant beneficial changes were observed on weight, BMI, blood pressure, glucose tolerance and serum lipids in any of the groups supplemented with cholecalciferol. We conclude that daily dose of 4000 IU cholecalciferol might be a useful adjunct in complex treatment of PCOS with fewer adverse events. Furthermore, pioglitazone and cholecalciferol combination seems to be marginally better although there was no statistical significance.

Keywords: PCOS, vitamin D supplementation, insulin resistance, spironolactone, metformin, pioglitazone

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Authors: Vemula Amalakrishna, S. Pushpavanam

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Change and motion characterize and persistently reshape the world around us, on scales from molecular to global. The subtle interplay between change (Reaction) and motion (Diffusion) gives rise to an astonishing intricate spatial or temporal pattern. These pattern formation in nature has been intellectually appealing for many scientists since antiquity. Periodic precipitation patterns, also known as Liesegang patterns (LP), are one of the stimulating examples of such self-assembling reaction-diffusion (RD) systems. LP formation has a great potential in micro and nanotechnology. So far, the research on LPs has been concentrated mostly on how these patterns are forming, retrieving information to build a universal mathematical model for them. Researchers have developed various theoretical models to comprehensively construct the geometrical diversity of LPs. To the best of our knowledge, simulation studies of LPs assume an arbitrary value of RD parameters to explain experimental observation qualitatively. In this work, existing models were studied to understand the mechanism behind this phenomenon and challenges pertaining to models were understood and explained. These models are not computationally effective due to the presence of discontinuous precipitation rate in RD equations. To overcome the computational challenges, smoothened Heaviside functions have been introduced, which downsizes the computational time as well. Experiments were performed using a conventional LP system (AgNO₃-K₂Cr₂O₇) to understand the effects of different gels and temperatures on formed LPs. The model is extended for real parameter values to compare the simulated results with experimental data for both 1-D (Cartesian test tubes) and 2-D(cylindrical and Petri dish).

Keywords: reaction-diffusion, spatio-temporal patterns, nucleation and growth, supersaturation

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Authors: Hyun-Jong Choi, Minjun Kwak, Doo-Won Seo, Sang-Kuk Woo, Sun-Dong Kim

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Solid Oxide Cell(SOC) systems can contribute to the transition to the hydrogen society by utilized as a power and hydrogen generator by the electrochemical reaction with high efficiency at high operation temperature (>750 ℃). La1-xSrxCo1-yFeyO3, which is an air electrode, is occurred stability degradations due to reaction and delamination with yittria stabilized zirconia(YSZ) electrolyte in a water electrolysis mode. To complement this phenomenon SOCs need gadolinium doped ceria(GDC) buffer layer between electrolyte and air electrode. However, GDC buffer layer requires a high sintering temperature and it causes a reaction with YSZ electrolyte. This study carried out low temperature sintering of GDC layer by applying Cu-oxide as a sintering aid. The effect of a copper additive as a sintering aid to lower the sintering temperature for the construction of solid oxide fuel cells (SOFCs) was investigated. GDC buffer layer with 0.25-10 mol% CuO sintering aid was prepared by reacting GDC power and copper nitrate solution followed by heating at 600 ℃. The sintering of CuO-added GDC powder was optimized by investigating linear shrinkage, microstructure, grain size, ionic conductivity, and activation energy of CuO-GDC electrolytes at temperatures ranging from 1100 to 1400 ℃. The sintering temperature of the CuO-GDC electrolyte decreases from 1400 ℃ to 1100 ℃ by adding the CuO sintering aid. The ionic conductivity of the CuO-GDC electrolyte shows a maximum value at 0.5 mol% of CuO. However, the addition of CuO has no significant effects on the activation energy of GDC electrolyte. GDC-LSCF layers were co-sintering at 1050 and 1100 ℃ and button cell tests were carried out at 750 ℃.

Keywords: Co-Sintering, GDC-LSCF, Sintering Aid, solid Oxide Cells

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