Search results for: drug policy

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: Shabnam Dadparvar, Laijin Shen

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This paper focuses on China’s policy in the Middle East and the rivalry with the U.S. The question is that what are the main factors on China’s Middle East policy and its competition with the U.S? The hypothesis regards to three effective factors: 'China’s energy dependency' on the Middle East, 'economy' and support for 'stability' in the Middle East. What is important in China’s competition with the U.S regarding to its Middle East policy is the substantial difference in ways of treating the countries of the region; China is committed to Westphalia model based on non-interference in internal affairs of the countries and respect the sovereignty of the governments. However, after 9/11, the U.S is seeking a balance between stability and change through intervention in the international affairs and in some cases is looking for a regime change. From the other hand, China, due to its dependency on the region’s energy welcomes America’s military presence in the region for providing stability. The authors by using a descriptive analytical method try to explain the situation of rivalry between China and the United States in Middle East. China is an 'emerging power' with high economic growth and in demand of more energy supply. The problem is that a rising power in the region is often a source of concern for hegemony.

Keywords: China's foreign policy, energy, hegemony, the Middle East

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Authors: Dimitrios J. Dimitriou

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Considering a worldwide tendency, air transports are growing very fast and many changes have taken place in planning, management and decision making process. Given the complexity of airport operation, the best use of existing capacity is the key driver of efficiency and productivity. This paper deals with the evaluation framework for the ground access at airports, by using a set of mode choice indicators providing key messages towards airport’s ground access performance. The application presents results for a sample of 12 European airports, illustrating recommendations to define policy and improve service for the air transport access chain.

Keywords: airport ground access, air transport chain, airport access performance, airport policy

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Authors: Fabien Candau, Florian Lafferrere

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This article analyses how an emission policy for vessels (named California’s Ocean-Going Vessel Fuel Rule) was implemented in 2009 in California impacts trade and marine biodiversity. By studying the decrease in emission levels anticipated by the policy, we measure not only the consequences for port activities but also for one of the most important marine ecosystems of the California Coast: the Kelp forests. Using the Difference in Difference (DiD) approach at the Californian ports level, we find that this policy has led to a significant decrease in trade volume during this period. Therefore, we find a positive and significant effect of shipping policy on kelp canopy and biomass growth by controlling the specific climatic and environmental characteristics of California coastal areas.

Keywords: international trade, shipping, marine biodiversity, emission control area

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Authors: Cameron Jones

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Emissions, produced by landfill waste from demolished obsolete buildings, have a damaging effect on both the Earth’s climate and human health. The philosophical theory of material vitalism - the potential for materials to react and emit harmful pollutants - therefore defines this construction and demolition waste (CDW) as having vitality. The European Union’s ‘Circular Economic Action Plan’ (CEAP) aims to mitigate the effects of CDW by prioritising the circularity of building materials. This dissertation examines how the philosophical theory of material vitalism can make an environmentally responsible contribution to CDW policy. The CEAP and Silvertown Quays development are used as case studies for the application of vitalism to policy revision. The study concludes that vitalism has a positive role to play in informing CDW policy, although its contribution is stronger in some areas. This is established by first appraising the aspects that relate to the obsolescence of buildings outlined in the EU’s existing CDW policies. Next, these policy directives are compared with the CE principles employed in the Silvertown Quays development. Subsequently, a keyword analysis model is used to categorise the language used in the CEAP, demonstrating how socio-political approaches to the CE and strategies to address resource scarcity could be strengthened to represent the EU’s policy aspirations more effectively. Recommendations are then made on how material vitalism could be utilised to strengthen legislation, arguing that a notable contribution can be made in most policy areas. Finally, theoretical testing of the impact of these revisions to policy on the case study development identified some practicalities for consideration in improving waste management outcomes.

Keywords: vitalism, construction waste, obsolescence, political ecology, exceptionalism

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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: Shabana Noureen, Zafar Mahmood

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Economies consistently engage in trade across borders and face tariff, non-tariff barriers and other quotas that constitute trade costs. The trade costs imposed by policy barriers on exports are considered an impediment in the export growth rate. This work aims to measure over-year trends in total and bilateral trade costs and their trends in relevance to policy barriers (tariff and non-tariff). The analysis through the micro-founded theoretically based gravity model showed that the total trade costs have a general decreasing trend in the world while in the case of developing countries, the rate by which these trends decline is very low. Bilateral trade cost estimates associated with the policy barriers represent that the non-tariff barriers in a developing country have a major role in sustaining the high trade costs as compared to the tariff barriers. This ultimately leads to a low net declining rate. This work emphasizes that for developing countries the non-tariff barriers are a major factor that renders their exports and to be uncompetitive in the world market.

Keywords: trade costs, policy barriers, tariff barriers, non-tariff barriers, trade policies, export growth

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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: Claudia Ehrentraut, Osama Ibrahim, Hercules Dalianis

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Policy making situations are real-world problems that exhibit complexity in that they are composed of many interrelated problems and issues. To be effective, policies must holistically address the complexity of the situation rather than propose solutions to single problems. Formulating and understanding the situation and its complex dynamics, therefore, is a key to finding holistic solutions. Analysis of text based information on the policy problem, using Natural Language Processing (NLP) and Text analysis techniques, can support modelling of public policy problem situations in a more objective way based on domain experts knowledge and scientific evidence. The objective behind this study is to support modelling of public policy problem situations, using text analysis of verbal descriptions of the problem. We propose a formal methodology for analysis of qualitative data from multiple information sources on a policy problem to construct a causal diagram of the problem. The analysis process aims at identifying key variables, linking them by cause-effect relationships and mapping that structure into a graphical representation that is adequate for designing action alternatives, i.e., policy options. This study describes the outline of an algorithm used to automate the initial step of a larger methodological approach, which is so far done manually. In this initial step, inferences about key variables and their interrelationships are extracted from textual data to support a better problem structuring. A small prototype for this step is also presented.

Keywords: public policy, problem structuring, qualitative analysis, natural language processing, algorithm, inference extraction

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Authors: Tianyu Chen

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China's school district education policy has encouraged parents to purchase properties in school districts with high-quality education resources. Shanghai has implemented "Simultaneous Admission to Public and Private Schools" (SAPPS) since 2018, which has covered all nine-year compulsory education by 2020. This study examines the impact of SAPPS on the housing market, specifically the premium effect of houses located in dual-school districts. Based on the Hedonic Pricing Model and the Signaling Theory, data is collected from 585 second-hand house transactions in Pudong New Area, Shanghai, and it is analyzed with the Difference-in-Differences (DID) model. The results indicate that the implementation of SAPPS has exacerbated the premium of dual school district housing and weakened the effect of the policy to a certain degree. To ensure equal access to education for all students, the government should work both on the supply and demand sides of the education resource equation.

Keywords: simultaneous admission to public and private schools, housing prices, education policy, education equity

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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: Hafez Abdo, Rob Ackrill

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Renewable energy (RE) promotion in the UK relies on multiple policy instruments, which are required to overcome the path dependency pressures favouring fossil fuels. These instruments include targeted funding schemes and economy-wide instruments embedded in the tax code. The resulting complexity of incentives raises important questions around the coherence and effectiveness of these instruments for RE generation. This complexity is exacerbated by UK RE policy being nested within EU policy in a multi-level governance (MLG) setting. To gain analytical traction on such complexity, this study will analyse policies promoting the on-farm generation of energy for heat and power, from farm and food waste, via anaerobic digestion. Utilising both primary and secondary data, it seeks to address a particular lacuna in the academic literature. Via a localised, in-depth investigation into the complexity of policy instruments promoting RE, this study will help our theoretical understanding of the challenges that MLG and path dependency pressures present to policymakers of multi-dimensional policies.

Keywords: anaerobic digestion, energy, green, policy, renewable, tax, UK

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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: W. Kongnoo, J. Loysongkroa, S. Chotivichien, N. Viriyautsahakul, N. Saiwongse

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Obesity, stunting and wasting problems among Thai school-aged children are increasing due to inappropriate food consumption behavior and poor environments for desirable nutritional behavior. Because of a low school lunch budget of only 0.40 USD per person per day, food quality is not up to nutritional standards. Therefore, the Health Department with the Education Ministry and the Thai Health Promotion Foundation have developed a quality school lunch project during 2009–2013. The program objectives were development and management of public policy to increase school lunch budget. The methods used a healthy public policy motivation process and movement in 241 local administrative organizations and 538 schools. The problem and solution research was organized to study school food and nutrition management, create a best practice policy mobilization model and hold a public hearing to motivate an increase of school meal funding. The results showed that local public policy has been motivated during 2009-2011 to increase school meal budget using local budgets. School children with best food consumption behavior and exercise increased from 13.2% in 2009 to 51.6% in 2013 and stunting decreased from 6.0% in 2009 to 4.7% in 2013. As the result of national policy motivation (2012-2013), the cabinet meeting on October 22, 2013 has approved an increase of school lunch budget from 0.40 USD to 0.62 USD per person per day. Thus, 5,800,469 school children nationwide have benefited from the budget increase.

Keywords: public policy, quality school lunch, Thailand, obesity

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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: 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: 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: Osiris Jorge Parcero, Néstor Gandelman, Flavia Roldán, Josef Montag

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This paper uses cross-country unbalanced panel data of up to 146 countries over the period 1996 to 2015 to be the first study to identify potential determinants of a country’s relative research output in Economics versus Business. More generally, it is also one of the first studies comparing Economics and Business. The results show that better policy-related data availability, higher income inequality, and lower ethnic fractionalization relatively favor economics. The findings are robust to two alternative fixed effects specifications, three alternative definitions of economics and business, two alternative measures of research output (publications and citations), and the inclusion of meaningful control variables. To the best of our knowledge, our paper is also the first to demonstrate the importance of policy-related data as drivers of economic research. Our regressions show that the availability of this type of data is the single most important factor associated with the prevalence of economics over business as a research domain. Thus, our work has policy implications, as the availability of policy-related data is partially under policy control. Moreover, it has implications for students, professionals, universities, university departments, and research-funding agencies that face choices between profiles oriented toward economics and those oriented toward business. Finally, the conclusions show potential lines for further research.

Keywords: research output, publication performance, bibliometrics, economics, business, policy-related data

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Authors: Mi Sun Park

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Biotechnology provides us with technological solutions to resource-based challenges facing the global society. A bioeconomy or bio-based economy emerged as all economic activities derived from biotechnology. This paper aims to understand discourses on bioeconomy in the sector of agriculture with three dimensions; media discourse, science discourse, and policy discourse. For achieving research goals, content analysis was applied to this research. Media articles, academic journal articles and policy documents published from 2000 to 2016 were collected in South Korea. The text was coded and analyzed with the categories of speakers and their arguments. The research findings indicate that powerful actors and key messages of bioeconomy in South Korean agriculture. Differences and similarities among media, science, and policy were examined. Therefore this case study can contribute to understanding dynamic interaction and interfaces of media, science and policy discourse on biotechnology in the sector of agriculture.

Keywords: media, discourse, bioeconomy, agriculture

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Authors: Shi Zhang

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This paper aims to introduce the allopatry of national college entrance examination which allow migrant students enter senior high schools and take college entrance exam where they live, identifies the reasons affect the implementation of this policy in the Chinese context. Most of China’s provinces and municipalities recently have announced new policies regarding national college entrance exams for non-local students. The paper conducts SWOT analysis reveals the opportunities, strength, weakness and challenges of the scheme, so as to discuss the implementation strategies from the perspectives of idea and institution. The research findings imply that the government should take a more positive attitude toward relaxing the allopatry of NCEE policy restrictions, and promote the reform household registration policy and NCEE policy with synchronous operations. Higher education institutions should explore the diversification of enrollment model; the government should issue the authority of universities and colleges to select elite migrant students beyond the restrictions of NCEE. To suit reform policies to local conditions, the big cities such as Beijing, Shanghai and Guangzhou should publish related compensate measures for children of migrant workers access to higher vocational colleges with tuition fee waivered. 

Keywords: college entrance examination, higher education, education policy, education equality

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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: T. Holecki, J. Wozniak-Holecka, K. Sobczyk

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Development, implementation, and evaluation of the effects of health policy programs, resulting from the identified health needs and health status of residents, is the own task of all local government units in Poland. This is due to the obligation to provide access to healthcare services to all residents and the implementation of tasks in the field of health promotion based on specific legal acts. Until the end of 2016 local governments financed health policy programs only with their own funds. Currently, there are additional resources available from the public health insurance subsidising up to 80% of health policy programs costs in cities with a population under 5 thousand people and up to 40% in bigger cities. Changes in legal provisions do not translate automatically to increased involvement of local government units in the implementation of public health tasks. The main objective of the study was to assess the actual impact of the new legal regulation on financing local health policy programs on the engagement of local administration in this area of public health activity. To achieve this aim, we analyzed difference in the number of local governments developing and implementing health policy programs before and after the new law came into force. The aim of the study was also to estimate the level of expenditures incurred by self-government units and the National Health Fund to cover the costs of health policy programs. In the first stage of the project, legal acts concerning the subject of research and financial data published by the National Health Fund were analyzed. The material for the second, main stage of the study was the detailed financial data obtained from the National Health Fund and data obtained from local government units. The results present the situation in Poland in territorial terms, divided into 16 voivodships.

Keywords: health care system, health policy programs, local self-governments, public health

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