Search results for: generic drug industry

Authors: Elena G. Salina, Laurent R. Chiarelli, Maria R. Pasca, Vadim A. Makarov

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Tuberculosis is one of the most challenging threats to human health, confronted by the problem of drug resistance. Evidently, new drugs for tuberculosis are urgently needed. Thienopyrimidine TP053 is one of the most promising new antitubercular prodrugs. Mycothiol-dependent reductase Mrx2, encoded by rv2466c, is known to be a TP053 activator; however, the precise mode of action of this compound remained unclear. Being highly active against both replicating and non-replicating tuberculosis bacilli, TP053 also revealed dose-escalating activity for M. tuberculosis-infected murine macrophages. The chemical structure of TP053 is characterized by the presence of NO₂ group which was suggested to be responsible for the toxic effects of the activated compound. Reduction of a nitroaromatic moiety of TP53 by Mrx2 was hypothesized to result in NO release. Analysis of the products of enzymatic activation of TP053 by Mrx2 by the Greiss reagent clearly demonstrated production of nitric oxide in a time-dependent manner. Mass-spectra of cell lysates of TP-treated M. tuberculosis bacilli demonstrated the transformation of TP053 to its non-active metabolite with Mw=261 that corresponds NO release. The mechanism of NO toxicity for bacteria includes DNA damage and degradation of iron-sulfur centers, especially under oxygen depletion. Thus, TP-053 drug-like scaffold is prospective for further development of novel anti-TB drug. This work was financially supported by the Russian Foundation for Basic Research (Grant 17-04-00342).

Keywords: drug discovery, M. tuberculosis, nitric oxide, NO donors

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Authors: Albert Gyamfi

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Cocoa plays critical role in the socio-economic development of Ghana. Meanwhile, smallholder farmers most of whom are illiterate dominate the industry. According to the cocoa-based agricultural knowledge and information system (AKIS) model knowledge is created and transferred to the industry between three key actors: cocoa researchers, extension experts, and cocoa farmers. Dwelling on the SECI model, the media richness theory (MRT), and the AKIS model, a conceptual model of web 2.0-based AKIS model (AKIS 2.0) is developed and used to assess the possible effects of social media usage for knowledge creation in the Ghanaian cocoa industry. A mixed method approach with a survey questionnaire was employed, and a second-order multi-group structural equation model (SEM) was used to analyze the data. The study concludes that the use of web 2.0 applications for knowledge creation would lead to sustainable interactions among the key knowledge actors for effective knowledge creation in the cocoa industry in Ghana.

Keywords: agriculture, cocoa, knowledge, media, web 2.0

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Authors: K. Yu Vlasova, M. A. Abakumov, H. Wishwarsao, M. Sokolsky, N. V. Nukolova, A. G. Majouga, Y. I. Golovin, N. L. Klyachko, A. V. Kabanov

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Introduction:Nowadays pharmaceutical medicine is aimed to create systems for combined therapy, diagnostic, drug delivery and controlled release of active molecules to target cells. Magnetic nanoparticles (MNPs) are used to achieve this aim. MNPs can be applied in molecular diagnostics, magnetic resonance imaging (T1/T2 contrast agents), drug delivery, hyperthermia and could improve therapeutic effect of drugs. The most common drug containers, containing MNPs, are liposomes, micelles and polymeric molecules bonded to the MNPs surface. Usually superparamagnetic nanoparticles are used (the general diameter is about 5-6 nm) and all effects of high frequency magnetic field (MF) application are based on Neel relaxation resulting in heating of surrounded media. In this work we try to develop a new method to improve drug release from MNPs under super low frequency MF. We suppose that under low frequency MF exposures the Brown’s relaxation dominates and MNPs rotation could occur leading to conformation changes and release of bioactive molecules immobilized on MNPs surface.The aim of this work was to synthesize different systems with active drug (biopolymers coated MNPs nanoclusters with immobilized enzymes and doxorubicin (Dox) loaded magnetic liposomes/micelles) and investigate the effect of super low frequency MF on these drug containers. Methods: We have synthesized MNPs of magnetite with magnetic core diameter 7-12 nm . The MNPs were coated with block-copolymer of polylysine and polyethylene glycol. Superoxide dismutase 1 (SOD1) was electrostatically adsorbed on the surface of the clusters. Liposomes were prepared as follow: MNPs, phosphatidylcholine and cholesterol were dispersed in chloroform, dried to get film and then dispersed in distillated water, sonicated. Dox was added to the solution, pH was adjusted to 7.4 and excess of drug was removed by centrifugation through 3 kDa filters. Results: Polylysine coated MNPs formed nanosized clusters (as observed by TEM) with intensity average diameter of 112±5 nm and zeta potential 12±3 mV. After low frequency AC MF exposure we observed change of immobilized enzyme activity and hydrodynamic size of clusters. We suppose that the biomolecules (enzymes) are released from the MNPs surface followed with additional aggregation of complexes at the MF in medium. Centrifugation of the nanosuspension after AC MF exposures resulted in increase of positive charge of clusters and change in enzyme concentration in comparison with control sample without MF, thus confirming desorption of negatively charged enzyme from the positively charged surface of MNPs. Dox loaded magnetic liposomes had average diameter of 160±8 nm and polydispersity index (PDI) 0.25±0.07. Liposomes were stable in DW and PBS at pH=7.4 at 370C during a week. After MF application (10 min of exposure, 50 Hz, 230 mT) diameter of liposomes raised to 190±10 nm and PDI was 0.38±0.05. We explain this by destroying and/or reorganization of lipid bilayer, that leads to changes in release of drug in comparison with control without MF exposure. Conclusion: A new application of low frequency AC MF for drug delivery and controlled drug release was shown. Investigation was supported by RSF-14-13-00731 grant, K1-2014-022 grant.

Keywords: magnetic nanoparticles, low frequency magnetic field, drug delivery, controlled drug release

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Authors: Alya A. Arabi

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Bioisosteres are functional groups that can be interchangeably used without affecting the potency of the drug. Bioisosteres have similar pharmacological properties. Bioisosterism is useful for modifying the physicochemical properties of a drug while obeying the Lipinski’s rules. Bioisosteres are key in optimizing the pharmacokinetic and pharmacodynamics properties of a drug. Tetrazole and carboxylate anions are non-classic bioisosteres. Density functional theory was used to obtain the wavefunction of the molecules and the optimized geometries. The quantum theory of atoms in molecules (QTAIM) was used to uncover the similarity of the average electron density in tetrazole and carboxylate anions. This similarity between the bioisosteres capped by a methyl group was valid despite the fact that the groups have different volumes, charges, energies, or electron populations. The biochemical correspondence of tetrazole and carboxylic acid was also determined to be a result of the similarity of the topography of the electrostatic potential (ESP). The ESP demonstrates the pharmacological and biochemical resemblance for a matching “key-and-lock” interaction.

Keywords: bioisosteres, carboxylic acid, density functional theory, electrostatic potential, tetrazole

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Authors: Yuxiang Pan, Yong Qiu, Chenlei Gu, Ping Wang

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In the past decade, three-dimensional (3D) tumor cell models have attracted increasing interest in the field of drug screening due to their great advantages in simulating more accurately the heterogeneous tumor behavior in vivo. Drug sensitivity testing based on 3D tumor cell models can provide more reliable in vivo efficacy prediction. The gold standard fluorescence staining is hard to achieve the real-time and label-free monitoring of the viability of 3D tumor cell models. In this study, micro-groove impedance sensor (MGIS) was specially developed for dynamic and non-invasive monitoring of 3D cell viability. 3D tumor cells were trapped in the micro-grooves with opposite gold electrodes for the in-situ impedance measurement. The change of live cell number would cause inversely proportional change to the impedance magnitude of the entire cell/matrigel to construct and reflect the proliferation and apoptosis of 3D cells. It was confirmed that 3D cell viability detected by the MGIS platform is highly consistent with the standard live/dead staining. Furthermore, the accuracy of MGIS platform was demonstrated quantitatively using 3D lung cancer model and sophisticated drug sensitivity testing. In addition, the parameters of micro-groove impedance chip processing and measurement experiments were optimized in details. The results demonstrated that the MGIS and 3D cell-based biosensor and would be a promising platform to improve the efficiency and accuracy of cell-based anti-cancer drug screening in vitro.

Keywords: micro-groove impedance sensor, 3D cell-based biosensors, 3D cell viability, micro-electromechanical systems

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Authors: Vipin Saini, Manish Kumar, Shailendra Bhatt, A. Pandurangan

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The aim of the present study was to fabricate a thermo sensitive gel containing Chlorpheniramine maleate (CPM) loaded nanoparticles following intranasal administration for effective treatment of allergic rhinitis. Chitosan based nanoparticles were prepared by precipitation method followed by the addition of developed NPs within the Poloxamer 407 and carbopol 934P based mucoadhesive thermo-reversible gel. Developed formulations were evaluated for Particle size, PDI, % entrapment efficiency and % cumulative drug permeation. NP3 formulation was found to be optimized on the basis of minimum particle size (143.9 nm), maximum entrapment efficiency (80.10±0.414 %) and highest drug permeation (90.92±0.531 %). The optimized formulation NP3 was then formulated into thermo reversible in situ gel. This intensifies the contact between nasal mucosa and the drug, increases and facilitates the drug absorption which results in increased bioavailability. G4 formulation was selected as the optimize on the basis of gelation ability and mucoadhesive strength. Histology was carried out to examine the damage caused by the optimized G4 formulation. Results revealed no visual signs of tissue damage thus indicated safe nasal delivery of nanoparticulate in situ gel formulation G4. Thus, intranasal CPM NP-loaded in situ gel was found to be a promising formulation for the treatment of allergic rhinitis.

Keywords: chitosan, nanoparticles, in situ gel, chlorpheniramine maleate, poloxamer 407

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Authors: Victoria I. Michailova, Denitsa B. Momekova, Hristiana A. Velichkova, Evgeni H. Ivanov

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The aim of this work is to design and develop thermo-responsive nanosized drug delivery systems based on poly(N-isopropylacrylamide)-g-poly(ethylene oxide) (PNIPAM-g-PEO) double hydrophilic graft copolymers. The PNIPAM-g-PEO copolymers are able to self-assemble in water into nanoparticles above the LCST of the thermo-responsive PNIPAM backbone and to disassemble and rapidly release the entrapped drugs upon cooling. However, their drug delivery applications are often hindered by their low loading capacity as the drugs to be encapsulated do not dissolve in water. In order to overcome this limitation, here we applied a low-temperature procedure with ethanol as an alternative route to the formation and loading a model hydrophobic drug, Indomethacin (IMC), into PNIPAM-g-PEO nanoparticles. The rationale for this approach was that ethanol dissolves both IMC and the copolymer and its mixing with water may induce micellization of PNIPAM-g-PEO at temperatures lower than the LCST. The influence of the volume fraction of ethanol and the temperature on the aggregation characteristics of PNIPAM-g-PEO copolymers (2.7 mol% PEO) was investigated by means of DLS, TEM and rheological dynamic oscillatory tests. The studies showed rich phase behavior at T < LCST, incl. the formation of highly solvated 500-1000 nm complex structures, 30-70 nm micelles and polymersomes as well as giant polymersomes, as the fraction of added ethanol increased. We believe that the PNIPAM-g-PEO self-assembly is favored due to the different solvation of its constituting blocks in ethanol-water mixtures. The incorporation of IMC led to alteration of the physicochemical and morphological characteristics of the blank nanoparticles. In this case, only monodisperse polymersomes and micelles were observed in the solutions with an average diameter less than 65 nm and substantial drug loading (DLC ~117 – 146 wt%). Indomethacin release from the nanoparticles was responsive to temperature changes, being much faster at a temperature of 42oC compared to that of 37oC under otherwise the same conditions. The results obtained suggest that these PNIPAM-g-PEO nanoparticles could be potential in mild hyper-thermic delivery of nonsteroidal anti-inflammatory drugs.

Keywords: drug delivery, nanoparticles, poly(N-isopropylacryl amide)-g-poly(ethylene oxide), thermo-responsive

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Authors: Megat Zuhairy, Megat Tajuddin, Hadijah Iberahim, Noraini Ismail

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This paper aims to discuss the impact of external networking on innovation and organizational performance in the construction industry. In Malaysia, the construction industry is known to be one of the industries that contribute significantly towards her economic growth. The construction industry is described as a fragmented and complex product system as construction projects implementation requires involvement of varying combination of large and small organizations across the supply chain spectrum. The innovation and performance of Malaysian construction industry are reported to be at underachieving and efforts for its improvement have inspired this study initiative. External networking among industry players is capable in bringing them to work together as a team, reducing the adversarial relationships among them for innovation effort and greater performance. The instrument in measuring innovation and organizational performance specific to the construction industry was developed by adapting measures introduced by several scholars in these fields. Contractors and consulting companies were the sampling frames of this study representing the construction industry in Malaysia. The population lists were developed from the lists provided by CIDB, BEM, BOA and BQSM. The samples were selected based on a stratified sampling method to gauge representation of the different groups in the population. Regression analysis was performed in this quantitative study to assess relationships amongst variables. The results revealed that principally, external networking is significant in influencing both innovation and organizational performance. Nevertheless, external networking with different industry players has a different impact on innovation and organizational performance. The study revealed that external networking with project players is significant on project performance but not on innovation. On the other hand, external networking with government agencies, academic institutions and professional bodies is significant in influencing innovation but not on organizational performance.

Keywords: innovation, external networking, organizational performance, construction industry

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Authors: Nuruddeen Usman, Usman Mohammed Gidado, Muhammad Ahmad Ibrahim

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Construction industry is one of the sectors that are eyeing adoption of ICT for its development due to the advancement in technology. Though, many manufacturing sectors had been using it, but construction industry was left behind, especially in the developing nation like Nigeria. On account of that, the objective of this study is to conceptually and quantitatively synthesise whether the slow adoption of ICT by the construction industries can be attributable to cybercrime threats. The result of the investigation found that, the risk of cybercrime, and lack of adequate cyber security policies that can enforce and punish defaulters are among the things that hinder ICT adoption of the Nigerian construction industries. Therefore, there is need for the nations to educate their citizens on cybercrime risk, and to establish cybercrime police units that can be monitoring and controlling all online communications.

Keywords: construction industry, cybercrime, information and communication technology adoption, risk

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Authors: Jagdish S. Patel, Piyush Chudasama

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Context: Over-expression of P-glycoprotein (P-gp) plays critical role in absorption of many drug candidates which results into lower bioavailability of the drug. P-glycoprotein also over expresses in many pathological conditions like diabetes, affecting the drug therapy. Modulation of P-gp expression using inhibitors can help in designing novel formulation enhancing the bioavailability of the drug in question. Objectives: The main focus of the study was to develop advanced glycation end products (AGEs) induced P-gp over expression in Caco-2 cells. Curcumin, piperine and epigallocatechin gallate were used to evaluate their P-gp inhibitory action using combinatorial approach. Materials and methods: Methylglyoxal (MG) induced P-gp over expression was checked in Caco-2 cells using real time PCR. P-gp inhibitory effects of the phytochemicals were measured after induction with MG alone and in combination of any two compounds. Cytotoxicity of each of the phytochemical was evaluated using MTT assay. Results: Induction with MG (100mM) significantly induced the over expression of P-glycoprotein in Caco-2 cells after 24 hr. Curcumin, piperine and epigallocatechin gallate alone significantly reduced the level of P-gp within 6 hr of treatment period monitored by real time PCR. The combination of any two phytochemical also down regulated the expression of P-gp in cells. Combinations of Curcumin and epigallocatechin gallate have shown significant down regulation when compared with other two combinations. Conclusions: Combinatorial approach for down regulating the expression of P-gp, in pathological conditions like diabetes, has demonstrated promising approach for therapeutic purpose.

Keywords: p-glycoprotein, curcumin, piperine, epigallocatechin gallate, p-gp inhibition

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Authors: Marvin Ricardo Awarab

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There has never been a greater need for telecom services. The Internet of Things (IoT), 5G networking, and edge computing are the driving forces behind this increased demand. The fierce demand offers communications service providers significant income opportunities. The telecom sector is centered on automation, and realizing a digital operation that functions as a real-time business will be crucial for the industry as a whole. Automation in telecom refers to the application of technology to create a more effective, quick, and scalable alternative to the conventional method of operating the telecom industry. With the promotion of 5G and the Internet of Things (IoT), telecom companies will continue to invest extensively in telecom automation technology. Automation offers benefits in the telecom industry; developing countries such as Namibia may not fully tap into such benefits because of the lack of funds and infrastructural resources to invest in automation. This paper fully investigates the benefits of automation in the telecom industry. Furthermore, the paper identifies hiccups that developing countries such as Namibia face in their quest to fully introduce automation in the telecom industry. Additionally, the paper proposes possible avenues that Namibia, as a developing country, adopt investing in automation infrastructural resources with the aim of reaping the full benefits of automation in the telecom industry.

Keywords: automation, development, internet, internet of things, network, telecom, telecommunications policy, 5G

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Authors: Farideh Gheitasi, Zahra Mirzaei Pour

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Considering mutual interactions of industry and residence in an environmental point of view is essential in effective urban management and all the policies must be made based on the results of these interactions. So, District No 21 of Tehran Municipality (Iran) which is almost industrial combined with some residential area was selected to study the consequences of industrial and residential area neighborhood. In this paper the results of two observations conducted in two timescales in 2010 and 2015, according to completed questionnaires by residents of an industrial region in the study area, were analyzed. The questionnaires contain 19 different environmental parameters considering positive and negative effects of industry on human life. The results of this study show that 96% of the target group in 2010 believed if the companies regard the law, mutual coexistence of industry and residency is possible. While this number decreased to 21% in 2015, which indicates that the problem got worse and people became more unsatisfied with the situation.

Keywords: environment, industry, residence, pollution

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Authors: Peter Burggräf, Moritz Krunke, Hanno Voet

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Due to shortening product and technology lifecycles, many companies use standardization approaches in product development and factory planning to reduce costs and time to market. Unlike large companies, where modular systems are already widely used, small and medium-sized companies often show a much lower degree of standardization due to lower scale effects and missing capacities for the development of these standards. To overcome these challenges, the development of industry sector specific standards in cooperations or by third parties is an interesting approach. This paper analyzes which branches that are mainly dominated by small or medium-sized companies might be especially interesting for the development of factory standards using the example of the German industry. For this, a key performance indicator based approach was developed that will be presented in detail with its specific results for the German industry structure.

Keywords: factory planning, factory standards, industry sector specific standardization, production planning

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Authors: Zhen Ye, Maryam Zaroudi, Elizabeth Aisenbrey, Nicolynn E. Davis, Peng Gao

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Nanoparticles have been used as drug delivery systems in the treatment of life-threatening diseases for decades, but traditional formulation development methods are time consuming and labor intensive. Millipore Sigma has developed a platform¬¬– NanoFabTxTM¬¬– for rapid and reproducible formulation development and screening to ensure consistentnanoparticle characteristics. Reproducible and precise control of the development process for a range of nanoparticle formulations accelerates the introduction of novel formulations to the clinic.

Keywords: Bio platform, Formulation development, NanoFabTxTM, Drug delivery

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Authors: Suhas Pednekar, Prashant Chavan, Ramesh Chaughule, Deepak Patkar

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Iron oxide (Fe3O4) magnetic nanoparticles (MNPs) are one of the most attractive nanomaterials for various biomedical applications. An important potential medical application of polymer-coated iron oxide nanoparticles (NPs) is as imaging agents. Composition, size, morphology and surface chemistry of these nanoparticles can now be tailored by various processes to not only improve magnetic properties but also affect the behavior of nanoparticles in vivo. MNPs are being actively investigated as the next generation of magnetic resonance imaging (MRI) contrast agents. Also, there is considerable interest in developing magnetic nanoparticles and their surface modifications with therapeutic agents. Our study involves the synthesis of biocompatible cancer drug coated with iron oxide nanoparticles and to evaluate their efficacy as MRI contrast agents. A simple and rapid microwave method to prepare Fe3O4 nanoparticles has been developed. The drug was successfully conjugated to the Fe3O4 nanoparticles which can be used for various applications. The relaxivity R2 (reciprocal of the spin-spin relaxation time T2) is an important factor to determine the efficacy of Fe nanoparticles as contrast agents for MRI experiments. R2 values of the coated magnetic nanoparticles were also measured using MRI technique and the results showed that R2 of the Fe complex consisting of Fe3O4, polymer and drug was higher than that of bare Fe nanoparticles and polymer coated nanoparticles. This is due to the increase in hydrodynamic sizes of Fe NPs. The results with various amounts of iron molar concentrations are also discussed. Using MRI, it is seen that the R2 relaxivity increases linearly with increase in concentration of Fe NPs in water.

Keywords: cancer drug, hydrodynamic size, magnetic nanoparticles, MRI

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Authors: Nichole Haag, Kimberly Velk, Tyler McCune, Chun Wu

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Methicillin/multiple-resistant Staphylococcus aureus (MRSA) are infectious bacteria that are resistant to common antibiotics. A previous in silico study in our group has identified a hypothetical protein SAV1226 as one of the potential drug targets. In this study, we reported the bioinformatics characterization, as well as cloning, expression, purification and kinetic assays of hypothetical protein SAV1226 from methicillin/vancomycin-resistant Staphylococcus aureus Mu50 strain. MALDI-TOF/MS analysis revealed a low degree of structural similarity with known proteins. Kinetic assays demonstrated that hypothetical protein SAV1226 is neither a domain of an ATP dependent dihydroxyacetone kinase nor of a phosphotransferase system (PTS) dihydroxyacetone kinase, suggesting that the function of hypothetical protein SAV1226 might be misannotated on public databases such as UniProt and InterProScan 5.

Keywords: Methicillin-resistant Staphylococcus aureus, dihydroxyacetone kinase, essential genes, drug target, phosphoryl group donor

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Authors: Papon Thamvasupong, Kwanchanok Viravaidya-Pasuwat

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Osteoarthritis affects a lot of people worldwide. Local injection of glucosamine is one of the alternative treatment methods to replenish the natural lubrication of cartilage. However, multiple injections can potentially lead to possible bacterial infection. Therefore, a drug delivery system is desired to reduce the frequencies of injections. A hydrogel is one of the delivery systems that can control the release of drugs. Thermo-reversible hydrogels can be beneficial to the drug delivery system especially in the local injection route because this formulation can change from liquid to gel after getting into human body. Once the gel is in the body, it will slowly release the drug in a controlled manner. In this study, various formulations of Pluronic-based hydrogels were synthesized for the controlled release of glucosamine. One of the challenges of the Pluronic controlled release system is its fast dissolution rate. To overcome this problem, alginate and calcium sulfate (CaSO₄) were added to the polymer solution. The characteristics of the hydrogels were investigated including the gelation temperature, gelation time, hydrogel dissolution and glucosamine release mechanism. Finally, a mathematical model of glucosamine release from Pluronic-alginate-hyaluronic acid hydrogel was developed. Our results have shown that crosslinking Pluronic gel with alginate did not significantly extend the dissolution rate of the gel. Moreover, the gel dissolution profiles and the glucosamine release mechanisms were best described using the zeroth-order kinetic model, indicating that the release of glucosamine was primarily governed by the gel dissolution.

Keywords: controlled release, drug delivery system, glucosamine, pluronic, thermoreversible hydrogel

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Authors: Abhay Asthana, Shally Toshkhani, Gyati Shilakari

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The present research was aimed to develop a biodegradable dermal patch formulation for wound healing in a novel, sustained and systematic manner. The goal is to reduce the frequency of dressings with improved drug delivery and thereby enhance therapeutic performance. In present study optimized formulation was designed using component polymers and excipients (e.g. Hydroxypropyl methyl cellulose, Ethylcellulose, and Gelatin) to impart significant folding endurance, elasticity and strength. Gelatin was used to get a mixture using ethylene glycol. Chitosan dissolved in suitable medium was mixed with stirring to gelatin mixture. With continued stirring to the mixture Curcumin was added in optimized ratio to get homogeneous dispersion. Polymers were dispersed with stirring in final formulation. The mixture was sonicated casted to get the film form. All steps were carried out under under strict aseptic conditions. The final formulation was a thin uniformly smooth textured film with dark brown-yellow color. The film was found to have folding endurance was around 20 to 21 times without a crack in an optimized formulation at RT (23C). The drug content was in range 96 to 102% and it passed the content uniform test. The final moisture content of the optimized formulation film was NMT 9.0%. The films passed stability study conducted at refrigerated conditions (4±0.2C) and at room temperature (23 ± 2C) for 30 days. Further, the drug content and texture remained undisturbed with stability study conducted at RT 23±2C for 45 and 90 days. Percentage cumulative drug release was found to be 80% in 12 h and matched the biodegradation rate as drug release with correlation factor R2 > 0.9. The film based formulation developed shows promising results in terms of stability and release profiles.

Keywords: biodegradable, patch, bioactive, polymer

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Authors: Sema Şenoğlu, Sevgi Karakuş

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Hydrazone scaffold is important to design new drug groups and is found to possess numerous uses in pharmaceutical chemistry. Besides, hydrazone derivatives are also known for biological activities such as anticancer, antimicrobial, antiviral, and antifungal. Hydrazone derivatives are promising anticancer agents because they inhibit cancer proliferation and induce apoptosis. Human carbonic anhydrase IX has a high potential to be an antiproliferative drug target, and targeting this protein is also important for obtaining potential anticancer inhibitors. The protein construct was retrieved as a PDB file from the RCSB protein database. This binding interaction of proteins and ligands was performed using Discovery Studio Visualizer. In vitro inhibitory activity of hydrazone derivatives was tested against enzyme carbonic anhydrase IX on the PyRx programme. Most of these molecules showed remarkable human carbonic anhydrase IX inhibitory activity compared to the acetazolamide. As a result, these compounds appear to be a potential target in drug design against human carbonic anhydrase IX.

Keywords: cancer, carbonic anhydrase IX enzyme, docking, hydrazone

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Authors: Junie B. Billones, Maria Constancia O. Carrillo, Voltaire G. Organo, Stephani Joy Y. Macalino, Inno A. Emnacen, Jamie Bernadette A. Sy

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One of the major interferences in the Philippines’ tuberculosis control program is the widespread prevalence of Mtb strains that are resistant to known drugs, such as the MDR-TB (Multi Drug Resistant Tuberculosis) and XDR-TB (Extensively Drug Resistant Tuberculosis). Therefore, there is a pressing need to search for novel Mtb drug targets in order to be able to combat these drug resistant strains. The enzyme 7,8-diaminopelargonic acid aminotransferase enzyme, or more commonly known as BioA, is one such ideal target, as it is known that humans do not possess this enzyme. BioA primarily plays a key role in Mtb’s lipid biosynthesis pathway; more specifically in the synthesis of the enzyme cofactor biotin. In this study, structure-based pharmacophore screening, docking, and ADMET evaluation of compounds obtained from the DrugBank chemical database were performed against the MtbBioA enzyme. Results of the screening, docking, ADMET, and TOPKAT calculations revealed that out of the 6,516 compounds in the library, only 7 compounds indicated more favorable binding energies as compared to the enzyme’s known inhibitor, amiclenomycin (ACM), as well as good solubility and toxicity properties. Moreover, out of these 7 compounds, Molecule 6 exhibited the best solubility and toxicity properties. In the future, these lead compounds may then be subjected to bioactivity assays in vitro or in vivo for further evaluation of its therapeutic efficacy.

Keywords: 7, 8-diaminopelargonic acid aminotransferase, BioA, pharmacophore, molecular docking, ADMET, TOPKAT

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Authors: Silvia Riva, Ezekiel Chinyio

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Introduction: Workers in different sectors are prone to stress at varying levels. They also respond to stress in different ways. An inspiration was to study stress development amongst workers in a work dangerous setting (Construction Industry) as well as how they cope with specific stress incidences. Objective: The overarching objective of the study was to study and correlate between stress and coping strategies. The research was conducted in an organizational industrial setting, and its findings on the coping actions of construction workers are reported in this article. Methods: An online cross-sectional survey was conducted with 80 participants aged 18-62. These were working for three different construction organizations in the West Midland region of the UK. Their coping actions were assessed using the COPE Inventory (Carver, 2013) instrument while the level of stress was assessed by the Perceived Stress Scale (Cohen, 1994). Results: Out of 80 workers (20 female, 25%, mean age 40.66), positive reinterpretation (M=4.15, SD=2.60) and active coping (M=4.18, SD=2.55) were the two most adaptive strategies reported by the workers while the most frequent maladaptive behavior was mental disengagement (M=3.62, SD=2.25). Among the maladaptive tactics, alcohol and drug abuse was a significant moderator in stress reactions (t=6.12, p=.000). Conclusion: Some maladaptive strategies are adopted by construction workers to cope with stress. So, it could be argued that programs of stress prevention and control in the construction industry have a basis to develop solutions that can improve and strengthen effective interventions when workers are stressed or getting stressed.

Keywords: coping, organization, strategies, stress

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Authors: Wessam H. Abd-Elsalam, Mona M. Saber, Samar M. Abouelatta

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Non-steroidal anti-inflammatory drugs (NSAIDs) are considered a double edged sword in inflammatory bowel diseases (IBDs). Some studies reported their advantageous effect in decreasing inflammation, and other studies reported that their use is associated with colitis aggravation. This study aimed to use specifically formulated trehalose-based nano-carriers that targets the colon in an attempt to alleviate inflammation caused by NSAIDs. L-α-phosphatidylcholine (PL), trehalose, and transcutol were used to prepare the trehalosomes (THs), which were also loaded with Tenoxicam(TXM) as a model NSAID. To optimize the formulation variables, a full 23 factorial design, using Design-Expert® software, was performed. The optimized formulation composed of trehalose: PL at a weight ratio of 1:1, 377.72 mg transcutol, and sonicated for 4 min, possessed a spherical shape with a size of 268.61 nm and EE% of 97.83% and released 70.22% of its drug content over 24 h. The superior protective action of TXM loaded THs compared to TXM suspension and drug-free THs was shown by the inhibition of the inflammatory biomarkers, namely; IL-1ß, IL-6, and TNF-alpha levels, as well as oxidative stress markers, measured as GSH and MDA. Improved histopathology of the colonic tissue in male New Zealand rabbits also confirmed the superiority of the TXM loaded THs compared to the unformulated drug or the drug free nano-carriers. Our findings highlight the prosperous role of THs in colon targeting and its anti-inflammatory characteristics in guarding against possible NSAIDs-driven exacerbation of colitis.

Keywords: inflammatory bowel disease, trehalose, trehalosomes, colon targeting

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Authors: Rudra Vaghela, P. K. Kulkarni

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The aim of the present research was to develop oral Amphotericin B (AmB) nanocrystals (Nc) grafted with suitable ligand in order to enhance drug transport across the intestinal epithelial barrier and subsequently, active uptake by macrophages. AmB Nc were prepared by liquid anti-solvent precipitation technique (LAS). Poloxamer 188 was used to stabilize the prepared AmB Nc and grafted with mannose for actively targeting M cells in Peyer’s patches. To prevent shedding of the stabilizer and ligand, N,N’-Dicyclohexylcarbodiimide (DCC) was used as a cross-linker. The prepared AmB Nc were characterized for particle size, PDI, zeta potential, X-ray diffraction (XRD) and surface morphology using scanning electron microscope (SEM) and evaluated for drug content, in vitro drug release and cell uptake studies using caco-2 cells. The particle size of stabilized AmB Nc grafted with WGA was in the range of 287-417 nm with negative zeta potential between -18 to -25 mV. XRD studies revealed crystalline nature of AmB Nc. SEM studies revealed that ungrafted AmB Nc were irregular in shape with rough surface whereas, grafted AmB Nc were found to be rod-shaped with smooth surface. In vitro drug release of AmB Nc was found to be 86% at the end of one hour. Cellular studies revealed higher invasion and uptake of AmB Nc towards caco-2 cell membrane when compared to ungrafted AmB Nc. Our findings emphasize scope on developing oral delivery system for passively targeting M cells in Peyer’s patches.

Keywords: leishmaniasis, amphotericin b nanocrystals, macrophage targeting, LAS technique

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Authors: Mehmood Faisal

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In this globalization era, the supply chain management has acquired strategic importance in diverse business environments. In the current highly competitive business environment, the success of any business considerably depends on the efficiency of the supply chain. The importance of petroleum industry cannot be avoided in the global market; however, supply chain management in the petroleum industry is facing various challenges, particularly in the logistics area. These logistical challenges have a main influence on the cost of crude oil; therefore, the opportunities to save cost in logistics still do exist. The large oil producing companies are undertaking future contracts through 'swaps or options' practice that saves their millions of dollars. The objective of this paper is to throw light on the supply chain challenges and opportunities in the oil industry and on swap practices which are widely employed by large oil producing companies around the world, such as Chevron Corporation, Saudi Arabian Oil Company, BP and Exxon Mobil.

Keywords: logistics, oil industry, swap practice, supply chain management

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Authors: Irfan Mohiuddin, Ahmad Al Mogren

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In recent years, cloud computing has earned substantial attention in the Oil and Gas Industry and provides services in all the phases of the industry lifecycle. Oil and gas supply infrastructure, in particular, is more vulnerable to accidental, natural and intentional threats because of its widespread distribution. Numerous surveys have been conducted on cloud security and privacy. However, to the best of our knowledge, hardly any survey is carried out that reviews cyber security in all phases with a cloud computing perspective. Moreover, a distinctive classification is performed for all the cloud-based cyber security measures based on the cloud component in use. The classification approach will enable researchers to identify the required technique used to enhance the security in specific cloud components. Also, the limitation of each component will allow the researchers to design optimal algorithms. Lastly, future directions are given to point out the imminent challenges that can pave the way for researchers to further enhance the resilience to cyber security threats in the oil and gas industry.

Keywords: cyber security, cloud computing, safety and security, oil and gas industry, security threats, oil and gas pipelines

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Authors: Dolly Gadhiya, Jayvadan Patel, Mihir Raval

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Lercanidipine hydrochloride is a calcium channel blockers used for treating angina pectoris and hypertension. Lercanidipine is a BCS Class II drug having poor aqueous solubility. Absolute bioavailability of Lercanidipine is very low and the main reason ascribed for this is poor aqueous solubility of the drug. Design and formulatation of nanocrystals by media milling method was main focus of this study. In this present study preliminary optimization was carried out with one factor at a time (OFAT) approach. For this different parameters like size of milling beads, amount of zirconium beads, types of stabilizer, concentrations of stabilizer, concentrations of drug, stirring speeds and milling time were optimized on the basis of particle size, polydispersity index and zeta potential. From the OFAT model different levels for above parameters selected for Plackett - Burman Design (PBD). Plackett-Burman design having 13 runs involving 6 independent variables was carried out at higher and lower level. Based on statistical analysis of PBD it was found that concentration of stabilizer, concentration of drug and stirring speed have significant impact on particle size, PDI, zeta potential value and saturation solubility. These experimental designs for preparation of nanocrystals were applied successfully which shows increase in aqueous solubility and dissolution rate of Lercanidipine hydrochloride.

Keywords: Lercanidipine hydrochloride, nanocrystals, OFAT, Plackett Burman

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Authors: Ana Caroline Ibrahim Lino, Denise Bomtempo Birche de Carvalho

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The background of this research is the international process of control and monitoring of illicit psychoactive substances that has commenced in the early 20th century. This process was intensified with the UN Single Convention on Narcotic Drugs of 1961 and had its culmination in the 1970s with the "War on drugs", a doctrine undertaken by the United States of America. Since then, the phenomenon of drug prohibition has been pushing debates around alternatives of public policies to confront their consequences at a global level and in the specific context of Latin America. Previous research has answered the following key questions: a) With what characteristics and models has the international illicit drug control system consolidated in Latin America with the creation of the Organization of American States (OAS) and the Inter-American Drug Abuse Control Commission (CICAD)? b) What drug policies and programs were determined as guidelines for the member states by the OAS and CICAD? The present paper mainly addresses the analysis of the drug strategies developed by the OAS/CICAD for the Americas from 2004 to 2016. The primary sources have been extracted from the OAS/CICAD documents and reports, listed on the Internet sites of these organizations. Secondary sources refer to bibliographic research on the subject with the following descriptors: illicit drugs, public policies, international organizations, OAS, CICAD, and reducing the demand and supply of illicit drugs. The "content analysis" technique was used to organize the collected material and to choose the axes of analysis. The results show that the policies, strategies, and action plans for Latin America had been focused on anti-drug actions since the creation of the Commission until 2010. The discourses and policies to reduce drug demand and supply were of great importance for solving the problem. However, the real focus was on eliminating the substances by controlling the production, marketing, and distribution of illicit drugs. Little attention was given to the users and their families. The research is of great relevance to the Social Work. The guidelines and parameters of the Social Worker's profession are in line with the need for social, ethical, and political strengthening of any dimension that guarantees the rights of users of psychoactive substances. In addition, it contributed to the understanding of the political, economic, social, and cultural factors that structure the prohibitionism, whose matrix anchors the deprivation of rights and violence.

Keywords: illicit drug policies, international organizations, latin America, prohibitionism, reduce the demand and supply of illicit drugs

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Authors: M. Naveed Yasin, Robert Brooke, Andrew Chan, Geoffrey I. N. Waterhouse, Drew Evans, Darren Svirskis, Ilva D. Rupenthal

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Poly(3,4-ethylenedioxythiophene) (PEDOT) is a robust conducting polymer (CP) exhibiting high conductivity and environmental stability. It can be synthesized by either chemical, electrochemical or vapour phase polymerization (VPP). Dexamethasone sodium phosphate (dexP) is an anionic drug molecule which has previously been loaded onto PEDOT as a dopant via electrochemical polymerisation; however this technique requires conductive surfaces from which polymerization is initiated. On the other hand, VPP produces highly organized biocompatible CP structures while polymerization can be achieved onto a range of surfaces with a relatively straight forward scale-up process. Following VPP of PEDOT, dexP can be loaded and subsequently released via ion-exchange. This study aimed at preparing and characterising both non-porous and porous VPP PEDOT structures including examining drug loading and release via ion-exchange. Porous PEDOT structures were prepared by first depositing a sacrificial polystyrene (PS) colloidal template on a substrate, heat curing this deposition and then spin coating it with the oxidant solution (iron tosylate) at 1500 rpm for 20 sec. VPP of both porous and non-porous PEDOT was achieved by exposing to monomer vapours in a vacuum oven at 40 mbar and 40 °C for 3 hrs. Non-porous structures were prepared similarly on the same substrate but without any sacrificial template. Surface morphology, compositions and behaviour were then characterized by atomic force microscopy (AFM), scanning electron microscopy (SEM), x-ray photoelectron spectroscopy (XPS) and cyclic voltammetry (CV) respectively. Drug loading was achieved by 50 CV cycles in a 0.1 M dexP aqueous solution. For drug release, each sample was exposed to 20 mL of phosphate buffer saline (PBS) placed in a water bath operating at 37 °C and 100 rpm. Film was stimulated (continuous pulse of ± 1 V at 0.5 Hz for 17 mins) while immersed into PBS. Samples were collected at 1, 2, 6, 23, 24, 26 and 27 hrs and were analysed for dexP by high performance liquid chromatography (HPLC Agilent 1200 series). AFM and SEM revealed the honey comb nature of prepared porous structures. XPS data showed the elemental composition of the dexP loaded film surface, which related well with that of PEDOT and also showed that one dexP molecule was present per almost three EDOT monomer units. The reproducible electroactive nature was shown by several cycles of reduction and oxidation via CV. Drug release revealed success in drug loading via ion-exchange, with stimulated porous and non-porous structures exhibiting a proof of concept burst release upon application of an electrical stimulus. A similar drug release pattern was observed for porous and non-porous structures without any significant statistical difference, possibly due to the thin nature of these structures. To our knowledge, this is the first report to explore the potential of VPP prepared PEDOT for stimuli-responsive drug delivery via ion-exchange. The produced porous structures were ordered and highly porous as indicated by AFM and SEM. These porous structures exhibited good electroactivity as shown by CV. Future work will investigate porous structures as nano-reservoirs to increase drug loading while sealing these structures to minimize spontaneous drug leakage.

Keywords: PEDOT for ion-exchange drug delivery, stimuli-responsive drug delivery, template based porous PEDOT structures, vapour phase polymerization of PEDOT

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Authors: Li Qiaoming

Abstract:

The outbreak of Coronavirus disease 2019 (COVID-19) in early 2020 brought new opportunities to the development of the digital creative industry in China. Based on the realistic foundation of the development of the digital creative industry in China, an analysis was conducted on the mechanism of action of the pandemic on this industry from both sides of supply and demand by sorting out its concept, connotation, and related theories. To be specific, the demand side experienced changes due to the changes in the consumption habits of residents, the sharp increase in gross domestic time (GDT), the satisfaction of the psychological needs of users, search for substitutes for offline consumption, and other factors. An analysis was carried out on the mechanism of action of the pandemic on the digital creative industry from the production link, supply subjects, product characteristics, and transmission link of the supply side. Then, a detailed discussion was held on the manifestation forms of the impact of the pandemic from the dimensions of time and space. Finally, this paper discussed the main development focuses of the digital creative industry in the post-pandemic era from the aspects of the government, industries, and enterprises.

Keywords: COVID-19, demand and supply relationship, digital creative industries, industry shocks

Procedia PDF Downloads 148

Authors: J. Jarolímek, P. Urban, P. Pavlínek, D. Dzúrová

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The industry constitutes a dominant economic sector in Czechia. The automotive industry represents the most important industrial sector in terms of gross value added and the number of employees. The objective of this study was to analyse the occurrence of occupational diseases (OD) in the automotive industry in Czechia during the 2001-2014 period. Whereas the occurrence of OD in other sectors has generally been decreasing, it has been increasing in the automotive industry, including growing spatial discrepancies. Data on OD cases were retrieved from the National Registry of Occupational Diseases. Further, we conducted a survey in automotive companies with a focus on occupational health services and positions of the companies in global production networks (GPNs). An analysis of OD distribution in the automotive industry was performed (age, gender, company size and its role in GPNs, regional distribution of studied companies, and regional unemployment rate), and was accompanied by an assessment of the quality and range of occupational health services. The employees older than 40 years had nearly 2.5 times higher probability of OD occurrence compared with employees younger than 40 years (OR 2.41; 95% CI: 2.05-2.85). The OD occurrence probability was 3 times higher for women than for men (OR 3.01; 95 % CI: 2.55-3.55). The OD incidence rate was increasing with the size of the company. An association between the OD incidence and the unemployment rate was not confirmed.

Keywords: occupational diseases, automotive industry, health geography, unemployment

Procedia PDF Downloads 247