Search results for: drug stability

Authors: Poteet Frances, Glovinski Ira

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INTRODUCTION: The interoceptive nervous system continuously senses chemical and anatomical changes and helps you recognize, understand, and feel what’s going on inside your body so it is important for energy regulation, memory, affect, and sense of self. A newborn needs predictable routines rather than confusion/chaos to make connections between internal experiences and emotions. AIM: Current legal protocols of removing babies from drug-addicted mothers impact the critical window of bonding. The newborn’s brain is social and the attachment process influences a child’s development which begins immediately after birth through nourishment, comfort, and protection. DESCRIPTION: Our project aims to educate drug-addicted mothers, and medical, nursing, and social work professionals on interoceptive concepts and practices to sustain the mother/newborn relationship. A mother’s interoceptive knowledge predicts children’s emotion regulation and social skills in middle childhood. CONCLUSION: When mothers develop an awareness of their inner bodily sensations, they can self-regulate and be emotionally available to co-regulate (support their newborn during distressing emotions and sensations). Our project has enhanced relationship preservation (mothers understand how their presence matters) and the overall mother/newborn connection.

Keywords: drug-addiction, interoception, legal, mothers, newborn, self-regulation

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Authors: Safari Mat Desa, Othman A. Karim, Mohd Kamarulhuda Samion, Saiful Bahri Hamzah

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Rubble mound breakwater was one of the most popular designs in Malaysia, constructed at the river mouth to dissipate the incoming wave energy from the seaward. Geometrically characteristics in trapezoid, crest width, and bottom width will determine the hypotonus stability, whilst structural height was designed for wave overtopping consideration. Physical hydraulic modelling in two-dimensional facilities was instigated in the flume to test the stability as well as the overtopping rate complied with the method of similarity, namely kinematic, dynamic, and geometric. Scaling effects of wave characteristics were carried out in order to acquire significant interaction of wave height, wave period, and water depth. Results showed two-dimensional physical modelling has proven reliable capability to ascertain breakwater stability significantly.

Keywords: breakwater, geometrical characteristic, wave overtopping, physical hydraulic modelling, method of similarity, wave characteristic

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Authors: Thanh Phuong Doan, Narueporn Sutanthavibul

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The influence of freezing cycle on influenza haemagglutinin (HA) conformational stability was investigated in terms of freezing rates and formulation compositions. The results showed that appropriate HA conformation could be evaluated using circular dichroism (CD) spectroscopy with HA concentration of greater than 0.09 mg/ml. The intermediate freezing rate of approximately 1.0oC/min preserved the original HA conformation better than at slow freezing rate (0.5oC/min) and rapid freezing rate (2.6oC/min). The changes in CD spectra of the secondary HA structure were more pronounced than those of the tertiary HA structure during the evaluation. Additionally, the formulations, which resulted in the highest conformational stability were found to have sucrose present in the composition. As opposed to when only glycine was used, the stability of HA conformation was poor.

Keywords: freezing, haemagglutinin, influenza, circular dichroism

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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: 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: Nurzaki Ikhsan, Ahmad Saifizul Abdullah, Rahizar Ramli

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One of the functions of the commercial heavy vehicle is to safely and efficiently transport goods and people. Due to its size and carrying capacity, it is important to study the vehicle dynamic stability during cornering. Study has shown that there are a number of overloaded heavy vehicles or permissible gross vehicle weight (GVW) violations recorded at selected areas in Malaysia assigned by its type and category. Thus, the objective of this study is to investigate the correlation and effect of the GVW on heavy vehicle stability during cornering event using simulation. Various selected heavy vehicle types and category are simulated using IPG/Truck Maker® with different GVW and road condition (coefficient of friction of road surface), while the speed, driver characteristic, center of gravity of load and road geometry are constant. Based on the analysis, the relationship between GVW and lateral acceleration were established. As expected, on the same value of coefficient of friction, the maximum lateral acceleration would be increased as the GVW increases.

Keywords: heavy vehicle, road safety, vehicle stability, lateral acceleration, gross vehicle weight

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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: B. D. Nkosi, T. F. Mutavhatsindi, J. J. Baloyi, R. Meeske, T. M. Langa, I. M. M. Malebana, M. D. Motiang

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Potato hash (PH), a by-product from food production industry, contains 188.4 g dry matter (DM)/kg and 3.4 g water soluble carbohydrate (WSC)/kg DM, and was mixed with wheat bran (70:30 as is basis) to provide 352 g DM/kg and 315 g WSC/kg DM. The materials were ensiled with or without silage additives in 1.5L anaerobic jars (3 jars/treatment) that were kept at 25-280 C for 3 months. Four types of silages were produced which were: control (no additive, denoted as T1), celluclast enzyme (denoted as T2), emsilage bacterial inoculant (denoted as T3) and silosolve bacterial inoculant (denoted as T4). Three jars per treatment were opened after 3 months of ensiling for the determination of nutritive values, fermentation characteristics and aerobic stability. Aerobic stability was done by exposing silage samples to air for 5 days. The addition of enzyme (T2) was reduced (P<0.05) silage pH, fiber fractions (NDF and ADF) while increasing (P < 0.05) residual WSC and lactic acid (LA) production, compared to other treatments. Silage produced had pH of < 4.0, indications of well-preserved silage. Bacterial inoculation (T3 and T4) improved (P < 0.05) aerobic stability of the silage, as indicated by increased number of hours and lower CO2 production, compared to other treatments. However, the aerobic stability of silage was worsen (P < 0.05) with the addition of an enzyme (T2). Further work to elucidate these effects on nutrient digestion and growth performance on ruminants fed the silage is needed.

Keywords: by-products, digestibility, feeds, inoculation, ruminants, silage

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Authors: Abdelhakam A. Noreldien, Sakhr B. Abudarag, Muslim S. Eltoum, Salih O. Osman

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This paper presents an analytical study of Small Unmanned Aerial Vehicle (SUAV) dynamic stability derivatives. Simulating SUAV dynamics and analyzing its behavior at the earliest design stages is too important and more efficient design aspect. The approach suggested in this paper is using the wind tunnel experiment to collect the aerodynamic data and get the dynamic stability derivatives. AutoCAD Software was used to draw the case study (wildlife surveillance SUAV). The SUAV is scaled down to be 0.25% of the real SUAV dimensions and converted to a wind tunnel model. The model was tested in three different speeds for three different attitudes which are; pitch, roll and yaw. The wind tunnel results were then used to determine the case study stability derivative values, and hence it used to calculate the roots of the characteristic equation for both longitudinal and lateral motions. Finally, the characteristic equation roots were found and discussed in all possible cases.

Keywords: model, simulating, SUAV, wind tunnel

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Authors: Anuar Ishak

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The mixed convection stagnation point flow toward a vertical plate is investigated. The external flow impinges normal to the heated plate and the surface temperature is assumed to vary linearly with the distance from the stagnation point. The governing partial differential equations are transformed into a set of ordinary differential equations, which are then solved numerically using MATLAB routine boundary value problem solver bvp4c. Numerical results show that dual solutions are possible for a certain range of the mixed convection parameter. A stability analysis is performed to determine which solution is linearly stable and physically realizable.

Keywords: dual solutions, heat transfer, mixed convection, stability analysis

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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: Kwang Chun, John Kemeny

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Light detection and ranging (LiDAR) has been a prevalent remote-sensing technology applied in the geological fields due to its high precision and ease of use. One of the major applications is to use the detailed geometrical information of underground structures as a basis for the generation of a three-dimensional numerical model that can be used in a geotechnical stability analysis such as FEM or DEM. To date, however, straightforward techniques in reconstructing the numerical model from the scanned data of the underground structures have not been well established or tested. In this paper, we propose a comprehensive approach integrating all the various processes, from LiDAR scanning to finite element numerical analysis. The study focuses on converting LiDAR 3D point clouds of geologic structures containing complex surface geometries into a finite element model. This methodology has been applied to Kartchner Caverns in Arizona, where detailed underground and surface point clouds can be used for the analysis of underground stability. Numerical simulations were performed using the finite element code Abaqus and presented by 3D computing visualization solution, ParaView. The results are useful in studying the stability of all types of underground excavations including underground mining and tunneling.

Keywords: finite element analysis, LiDAR, remote-sensing, scientific visualization, underground stability

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Authors: Sunita Makchuchit, Arunporn Itharat

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Prasaprohyai, a Thai traditional medicine preparation listed in the Thai National List of Essential Medicines, is commonly used for treatment of fever and colds. Prasaprohyai preparation consists of 21 different plants, with Kaempferia galanga (50% w/w) as the main ingredient. The objective of this study was to investigate the anti-allergic activity of the crude extract from Prasaprohyai after accelerated stability test procedure. The method of extract used maceration in 95% ethanol and the crude extract was kept under accelerated condition at 40 ± 2 oC and 75 ± 5% relative humidity (RH) for six months. After six months of storage at 40 oC, the crude sample in various storage times (0, 15, 30, 45, 60, 90, 120, 150 and 180 days) were investigated for anti-allergic activity using IgE-sensitized RBL-2H3 cell lines. The results showed that the stability of crude ethanolic extract from Prasaprohyai under accelerated testing had no significant effect of anti-allergic activity when compared with day 0. The results showed that the ethanolic extract could be stored for two years at room temperature without loss of activity.

Keywords: accelerated stability, anti-allergy, prasaprohyai, RBL-2H3 cell lines

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Authors: Pemika Ketsuwan, Pitt Supaphol, Manit Nithitanakul

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A typical used of ethylene methyl acrylate (EMA) gasket is in the manufacture of optical lens, and often, they are deteriorated rapidly due to high temperature during the process. The objective of this project is to improve the thermal stability of the EMA copolymer gasket by preparing EMA with cellulose and silica composites. Hydroxy propyl methyl cellulose (HPMC) and Carboxy methyl cellulose (CMC) were used in preparing of EMA/cellulose composites and fumed silica (SiO2) was used in preparing EMA/silica composites with different amounts of filler (3, 5, 7, 10, 15 wt.%), using a twin screw extruder at 160 °C and the test specimens were prepared by the injection molding machine. The morphology and dispersion of fillers in the EMA matrix were investigated by field emission scanning electron microscopy (FESEM). The thermal stability of the composite was determined by thermal gravimetric analysis (TGA), and differential scanning calorimeter (DSC). Mechanical properties were evaluated by tensile testing. The developed composites were found to enhance thermal and mechanical properties when compared to that of the EMA copolymer alone.

Keywords: ethylene methyl acrylate, HPMC, Silica, Thermal stability

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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: 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: Mouna Baassi, Mohamed Moussaoui, Hatim Soufi, Sanchaita RajkhowaI, Ashwani Sharma, Subrata Sinha, Said Belaaouad

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Human Immunodeficiency Virus type 1 protease (HIV-1 PR) is one of the most challenging targets of antiretroviral therapy used in the treatment of AIDS-infected people. The performance of protease inhibitors (PIs) is limited by the development of protease mutations that can promote resistance to the treatment. The current study was carried out using statistics and bioinformatics tools. A series of thirty-three compounds with known enzymatic inhibitory activities against HIV-1 protease was used in this paper to build a mathematical model relating the structure to the biological activity. These compounds were designed by software; their descriptors were computed using various tools, such as Gaussian, Chem3D, ChemSketch and MarvinSketch. Computational methods generated the best model based on its statistical parameters. The model’s applicability domain (AD) was elaborated. Furthermore, one compound has been proposed as efficient against HIV-1 protease with comparable biological activity to the existing ones; this drug candidate was evaluated using ADMET properties and Lipinski’s rule. Molecular Docking performed on Wild Type and Mutant Type HIV-1 proteases allowed the investigation of the interaction types displayed between the proteases and the ligands, Darunavir (DRV) and the new drug (ND). Molecular dynamics simulation was also used in order to investigate the complexes’ stability, allowing a comparative study of the performance of both ligands (DRV & ND). Our study suggested that the new molecule showed comparable results to that of Darunavir and may be used for further experimental studies. Our study may also be used as a pipeline to search and design new potential inhibitors of HIV-1 proteases.

Keywords: QSAR, ADMET properties, molecular docking, molecular dynamics simulation.

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Authors: Kongrat Nokkaew

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This article assessed the surface erosion and stability of cut and fill slope in the excavation of the detention basin, Kalasin Province, Thailand. The large excavation project was built to enlarge detention basin for relieving repeated flooding and drought which usually happen in this area. However, at the end of the 1st rainstorm season, severely erosions slope failures were widespread observed. After investigation, the severity of erosions and slope failure were classified into five level from sheet erosion (Level 1), rill erosion (Level 2, 3), gully erosion (Level 4), and slope failure (Level 5) for proposing slope remediation. The preliminary investigation showed that lack of runoff control were the major factors of the surface erosions while insufficient compacted of the fill slope leaded to slopes failures. The slope stability of four selected slope failure was back calculated by using Simplified Bishop with Seep-W. The result show that factor of safety of slope located on non-plasticity sand was less than one, representing instability of the embankment slope. Such analysis agreed well with the failures observed in the field.

Keywords: surface erosion, slope stability, detention basin, cut and fill

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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: Meenu Mehta, Munish Garg

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The use of oral anticancer drugs from AYUSH system of medicine is widely increased among the society due to their low cost, enhanced efficacy, increased patient preference, lack of inconveniences related to infusion and they provide an opportunity to develop chronic treatment regimens. However, oral delivery of these drugs usually laid down by the limited bioavailability of the drug, which is associated with a wide variation. As most of the cytotoxic agents have a narrow therapeutic window and are dosed at or near the maximum tolerated dose, a wide variability in the bioavailability can negatively affect treatment result. It is estimated that 40% of active substances are poorly soluble in water. The improvement of bio-availability of drugs with such properties presents one of the greatest challenges in drug formulations. There are several techniques reported in literature. Among all these Self Emulsifying Drug Delivery System (SEDDS) has gained more attention due to enhanced oral bio-availability enabling a reduction in dose. Thus, SEDDS anticancer drugs will have the increased bioavailability and efficacy. These dosage form will provide societal benefit in a cost-effective manner as compared to other oral dosage forms. Present study reflects on the formulation strategies as SEDDS for oral anticancer agents of AYUSH system for enhanced bioavailability with proven efficacy by cancer cell lines.

Keywords: anticancer agents, AYUSH system, bioavailability, SEDDS

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