Search results for: multi drug resistant

Authors: Danilo A. F. Fontes, Magaly A. M.Lyra, Maria L. C. Moura, Leslie R. M. Ferraz, Salvana P. M. Costa, Amanda C. Q. M. Vieira, Larissa A. Rolim, Giovanna C. R. M. Schver, Ping I. Lee, Severino Alves-Júnior, José L. Soares-Sobrinho, Pedro J. Rolim-Neto

Abstract:

Efavirenz (EFV) is a first-choice drug in antiretroviral therapy with high efficacy in the treatment of infection by Human Immunodeficiency Virus, which causes Acquired Immune Deficiency Syndrome (AIDS). EFV has low solubility in water resulting in a decrease in the dissolution rate and, consequently, in its bioavailability. Among the technological alternatives to increase solubility, the Lamellar Double Hydroxides (LDH) have been applied in the development of systems with poorly water-soluble drugs. The use of analytical techniques such as X-Ray Diffraction (XRD), Infrared Spectroscopy (IR) and Differential Scanning Calorimetry (DSC) allowed the elucidation of drug interaction with the lamellar compounds. The objective of this work was to characterize and develop the binary systems with EFV and LDH in order to increase the solubility of the drug. The LDH-CaAl was synthesized by the method of co-precipitation from salt solutions of calcium nitrate and aluminum nitrate in basic medium. The systems EFV-LDH and their physical mixtures (PM) were obtained at different concentrations (5-60% of EFV) using the solvent technique described by Takahashi & Yamaguchi (1991). The characterization of the systems and the PM’s was performed by XRD techniques, IR, DSC and dissolution test under non-sink conditions. The results showed improvements in the solubility of EFV when associated with LDH, due to a possible change in its crystal structure and formation of an amorphous material. From the DSC results, one could see that the endothermic peak at 173°C, temperature that correspond to the melting process of EFZ in the crystal form, was present in the PM results. For the EFZ-LDH systems (with 5, 10 and 30% of drug loading), this peak was not observed. XRD profiles of the PM showed well-defined peaks for EFV. Analyzing the XRD patterns of the systems, it was found that the XRD profiles of all the systems showed complete attenuation of the characteristic peaks of the crystalline form of EFZ. The IR technique showed that, in the results of the PM, there was the appearance of one band and overlap of other bands, while the IR results of the systems with 5, 10 and 30% drug loading showed the disappearance of bands and a few others with reduced intensity. The dissolution test under non-sink conditions showed that systems with 5, 10 and 30% drug loading promoted a great increase in the solubility of EFV, but the system with 10% of drug loading was the only one that could keep substantial amount of drug in solution at different pHs.

Keywords: Efavirenz, Lamellar Double Hydroxides, Pharmaceutical Techonology, Solubility

Procedia PDF Downloads 560

Authors: Mustafa Al Sukar, Azzam Sleit, Abdullatif Abu-Dalhoum, Bassam Al-Kasasbeh

Abstract:

Use and abuse of drugs by teens is very common and can have dangerous consequences. The drugs contribute to physical and sexual aggression such as assault or rape. Some teenagers regularly use drugs to compensate for depression, anxiety or a lack of positive social skills. Teen resort to smoking should not be minimized because it can be "gateway drugs" for other drugs (marijuana, cocaine, hallucinogens, inhalants, and heroin). The combination of teenagers' curiosity, risk taking behavior, and social pressure make it very difficult to say no. This leads most teenagers to the questions: "Will it hurt to try once?" Nowadays, technological advances are changing our lives very rapidly and adding a lot of technologies that help us to track the risk of drug abuse such as smart phones, Wireless Sensor Networks (WSNs), Internet of Things (IoT), etc. This technique may help us to early discovery of drug abuse in order to prevent an aggravation of the influence of drugs on the abuser. In this paper, we have developed a Decision Support System (DSS) for detecting the drug abuse using Artificial Neural Network (ANN); we used a Multilayer Perceptron (MLP) feed-forward neural network in developing the system. The input layer includes 50 variables while the output layer contains one neuron which indicates whether the person is a drug addict. An iterative process is used to determine the number of hidden layers and the number of neurons in each one. We used multiple experiment models that have been completed with Log-Sigmoid transfer function. Particularly, 10-fold cross validation schemes are used to access the generalization of the proposed system. The experiment results have obtained 98.42% classification accuracy for correct diagnosis in our system. The data had been taken from 184 cases in Jordan according to a set of questions compiled from Specialists, and data have been obtained through the families of drug abusers.

Keywords: drug addiction, artificial neural networks, multilayer perceptron (MLP), decision support system

Procedia PDF Downloads 276

Authors: Monika Patel, Kazuaki Matsumura

Abstract:

Synthetic hydrogels, with their unique properties such as porosity, strength, and swelling in aqueous environment, are being used in many fields from food additives to regenerative medicines, from diagnostic and pharmaceuticals to drug delivery systems (DDS). But, hydrogels also have some limitations in terms of homogeneity of drug distribution and quantity of loaded drugs. As an alternate, polymeric micelles are extensively used as DDS. With the ease of self-assembly, and distinct stability they remarkably improve the solubility of hydrophobic drugs. However, presently, combinational therapy is the need of time and so are systems which are capable of releasing more than one drug. And it is one of the major challenges towards DDS to control the release of each drug independently, which simple DDS cannot meet. In this work, we present an amphiphilic polypeptide based micelle hydrogel composite to study the dual drug release for wound healing purposes using Amphotericin B (AmpB) and Curcumin as model drugs. Firstly, two differently charged amphiphilic polypeptide chains were prepared namely, poly L-Lysine-b-poly phenyl alanine (PLL-PPA) and poly Glutamic acid-b-poly phenyl alanine (PGA-PPA) through ring opening polymerization of amino acid N-carboxyanhydride. These polymers readily self-assemble to form micelles with hydrophobic PPA block as core and hydrophilic PLL/PGA as shell with an average diameter of about 280nm. The thus formed micelles were loaded with the model drugs. The PLL-PPA micelle was loaded with curcumin and PGA-PPA was loaded with AmpB by dialysis method. Drug loaded micelles showed a slight increase in the mean diameter and were fairly stable in solution and lyophilized forms. For forming the micelles hydrogel composite, the drug loaded micelles were dissolved and were cross linked using genipin. Genipin uses the free –NH2 groups in the PLL-PPA micelles to form a hydrogel network with free PGA-PPA micelles trapped in between the 3D scaffold formed. Different composites were tested by changing the weight ratios of the both micelles and were seen to alter its resulting surface charge from positive to negative with increase in PGA-PPA ratio. The composites with high surface charge showed a burst release of drug in initial phase, were as the composites with relatively low net charge showed a sustained release. Thus the resultant surface charge of the composite can be tuned to tune its drug release profile. Also, while studying the degree of cross linking among the PLL-PPA particles for effect on dual drug release, it was seen that as the degree of crosslinking increases, an increase in the tendency to burst release the drug (AmpB) is seen in PGA-PPA particle, were as on the contrary the PLL-PPA particles showed a slower release of Curcumin with increasing the cross linking density. Thus, two different pharmacokinetic profile of drugs were seen by changing the cross linking degree. In conclusion, a unique charged amphiphilic polypeptide based micelle hydrogel composite for dual drug delivery. This composite can be finely tuned on the basis of need of drug release profiles by changing simple parameters such as composition, cross linking and pH.

Keywords: amphiphilic polypeptide, dual drug release, micelle hydrogel composite, tunable DDS

Procedia PDF Downloads 187

Authors: Nitin Jadhav, Pradeep R. Vavia

Abstract:

Poor water soluble drugs are difficult to promote for oral drug delivery as they demonstrate poor and variable bioavailability because of its poor solubility and dissolution in GIT fluid. Nowadays lipid based formulations especially self microemulsifying drug delivery system (SMEDDS) is found as the most effective technique. With all the impressive advantages, the need of high amount of surfactant (50% - 80%) is the major drawback of SMEDDS. High concentration of synthetic surfactant is known for irritation in GIT and also interference with the function of intestinal transporters causes changes in drug absorption. Surfactant may also reduce drug activity and subsequently bioavailability due to the enhanced entrapment of drug in micelles. In chronic treatment these issues are very conspicuous due to the long exposure. In addition the liquid self microemulsifying system also suffers from stability issues. Recently one novel approach of solid stabilized micro and nano emulsion (Pickering emulsion) has very admirable properties such as high stability, absence or very less concentration of surfactant and easily converts into the dry form. So here we are exploring pickering dry emulsion system for dissolution enhancement of anti-lipemic, extremely poorly water soluble drug (Fenofibrate). Oil moiety for emulsion preparation was selected mainly on the basis of higher solubility of drug. Captex 300 was showed higher solubility for fenofibrate, hence selected as oil for emulsion. With Silica (solid stabilizer); Span 20 was selected to improve the wetting property of it. Emulsion formed by Silica and Span20 as stabilizer at the ratio 2.5:1 (silica: span 20) was found very stable at the particle size 410 nm. The prepared emulsion was further preceded for spray drying and formed microcapsule evaluated for in-vitro dissolution study, in-vivo pharmacodynamic study and characterized for DSC, XRD, FTIR, SEM, optical microscopy etc. The in vitro study exhibits significant dissolution enhancement of formulation (85 % in 45 minutes) as compared to plain drug (14 % in 45 minutes). In-vivo study (Triton based hyperlipidaemia model) exhibits significant reduction in triglyceride and cholesterol with formulation as compared to plain drug indicating increasing in fenofibrate bioavailability. DSC and XRD study exhibit loss of crystallinity of drug in microcapsule form. FTIR study exhibit chemical stability of fenofibrate. SEM and optical microscopy study exhibit spherical structure of globule coated with solid particles.

Keywords: captex 300, fenofibrate, pickering dry emulsion, silica, span20, stability, surfactant

Procedia PDF Downloads 484

Authors: S. H. Gasa, L. Singh, B. Pillay, A. O. Olaniran

Abstract:

Wastewater treatment plants (WWTPs) have been implicated as the leading reservoir for antibiotic resistant bacteria (ARB), including Enterococci spp. and antibiotic resistance genes (ARGs), worldwide. Enterococci are a group of clinically significant bacteria that have gained much attention as a result of their antibiotic resistance. They play a significant role as the principal cause of nosocomial infections and dissemination of antimicrobial resistance genes in the environment. The main objective of this study was to ascertain the role of WWTPs in Durban, South Africa as potential reservoirs for antibiotic resistant Enterococci (ARE) and their related ARGs. Furthermore, the antibiogram and resistance gene profile of Enterococci species recovered from treated wastewater effluent and receiving surface water in Durban were also investigated. Using membrane filtration technique, Enterococcus selective agar and selected antibiotics, ARE were enumerated in samples (influent, activated sludge, before chlorination and final effluent) collected from two WWTPs, as well as from upstream and downstream of the receiving surface water. Two hundred Enterococcus isolates recovered from the treated effluent and receiving surface water were identified by biochemical and PCR-based methods, and their antibiotic resistance profiles determined by the Kirby-Bauer disc diffusion assay, while PCR-based assays were used to detect the presence of resistance and virulence genes. High prevalence of ARE was obtained at both WWTPs, with values reaching a maximum of 40%. The influent and activated sludge samples contained the greatest prevalence of ARE with lower values observed in the before and after chlorination samples. Of the 44 vancomycin and high-level gentamicin-resistant isolates, 11 were identified as E. faecium, 18 as E. faecalis, 4 as E. hirae while 11 are classified as “other” Enterococci species. High-level aminoglycoside resistance for gentamicin (39%) and vancomycin (61%) was recorded in species tested. The most commonly detected virulence gene was the gelE (44%), followed by asa1 (40%), while cylA and esp were detected in only 2% of the isolates. The most prevalent aminoglycoside resistance genes were aac(6')-Ie-aph(2''), aph(3')-IIIa, and ant(6')-Ia detected in 43%, 45% and 41% of the isolates, respectively. Positive correlation was observed between resistant phenotypes to high levels of aminoglycosides and presence of all aminoglycoside resistance genes. Resistance genes for glycopeptide: vanB (37%) and vanC-1 (25%), and macrolide: ermB (11%) and ermC (54%) were detected in the isolates. These results show the need for more efficient wastewater treatment and disposal in order to prevent the release of virulent and antibiotic resistant Enterococci species and safeguard public health.

Keywords: antibiogram, enterococci, gentamicin, vancomycin, virulence signatures

Procedia PDF Downloads 196

Authors: Feng-Tsai Weng, Rick Wang, Yan-Cong Liao

Abstract:

Passivation is a kind of surface treatment for material to reinforce the corrosion resistance specially the stainless alloy. Passive film, is to getting more potential compared to their status before passivation. An oxidation film can be formed on the surface of stainless steel, which has a strong corrosion resistance ability after passivation treatment. In this research, a new passivation technology is proposed for a special stainless alloy which contains a 12-14% Chromium. This method includes the A-A-A (alkaline-acid-alkaline) process basically, which was developed by Carpenter that can neutralize trapped acid. Besides, a corrosion resistant coating layer was obtained by immersing the parts in a water bath of mineral oil at high temperature. Salt spray test ASTM B368 was conducted to investigated performance of corrosion resistant of the passivated stainless steel alloy parts. Results show much better corrosion resistant that followed a coating process after A-A-A Passivation process, than only using A-A-A process. The passivation time is with more than 380 hours of salt spray test ASTM B368, which is equal to 3000 hours of Salt spray test ASTM B117. Proposed passivation method of stainless steel can be completed in about 3 hours.

Keywords: passivation, alkaline-acid-alkaline, stainless steel, salt spray test

Procedia PDF Downloads 341

Authors: Bo Wang

Abstract:

The geometric processing of multi-source remote sensing data using control data of different scale and different accuracy is an important research direction of multi-platform system for earth observation. In the existing block bundle adjustment methods, as the controlling information in the adjustment system, the approach using single observation scale and precision is unable to screen out the control information and to give reasonable and effective corresponding weights, which reduces the convergence and adjustment reliability of the results. Referring to the relevant theory and technology of quotient space, in this project, several subjects are researched. Multi-layer quotient space of multi-geometric features is constructed to describe and filter control data. Normalized granularity merging mechanism of multi-layer control information is studied and based on the normalized scale factor, the strategy to optimize the weight selection of control data which is less relevant to the adjustment system can be realized. At the same time, geometric positioning experiment is conducted using multi-source remote sensing data, aerial images, and multiclass control data to verify the theoretical research results. This research is expected to break through the cliché of the single scale and single accuracy control data in the adjustment process and expand the theory and technology of photogrammetry. Thus the problem to process multi-source remote sensing data will be solved both theoretically and practically.

Keywords: multi-source image geometric process, high precision geometric positioning, quotient space of multi-geometric features, optimized weight selection

Procedia PDF Downloads 260

Authors: Inês N. Peça , A. Bicho, Rui Gardner, M. Margarida Cardoso

Abstract:

Inorganic/organic nanocomplexes offer tremendous scope for future biomedical applications, including imaging, disease diagnosis and drug delivery. The combination of Fe3O4 with biocompatible polymers to produce smart drug delivery systems for use in pharmaceutical formulation present a powerful tool to target anti-cancer drugs to specific tumor sites through the application of an external magnetic field. In the present study, we focused on the evaluation of the effect of the magnetic field application time on the rate of drug release from iron oxide polymeric nanoparticles. Doxorubicin, an anticancer drug, was selected as the model drug loaded into the nanoparticles. Nanoparticles composed of poly(d-lactide-co-glycolide (PLGA), a biocompatible polymer already approved by FDA, containing iron oxide nanoparticles (MNP) for magnetic targeting and doxorubicin (DOX) were synthesized by the o/w solvent extraction/evaporation method and characterized by scanning electron microscopy (SEM), by dynamic light scattering (DLS), by inductively coupled plasma-atomic emission spectrometry and by Fourier transformed infrared spectroscopy. The produced particles yielded smooth surfaces and spherical shapes exhibiting a size between 400 and 600 nm. The effect of the magnetic doxorubicin loaded PLGA nanoparticles produced on cell viability was investigated in mammalian CHO cell cultures. The results showed that unloaded magnetic PLGA nanoparticles were nontoxic while the magnetic particles without polymeric coating show a high level of toxicity. Concerning the therapeutic activity doxorubicin loaded magnetic particles cause a remarkable enhancement of the cell inhibition rates compared to their non-magnetic counterpart. In vitro drug release studies performed under a non-permanent magnetic field show that the application time and the on/off cycle duration have a great influence with respect to the final amount and to the rate of drug release. In order to determine the mechanism of drug release, the data obtained from the release curves were fitted to the semi-empirical equation of the the Korsmeyer-Peppas model that may be used to describe the Fickian and non-Fickian release behaviour. Doxorubicin release mechanism has shown to be governed mainly by Fickian diffusion. The results obtained show that the rate of drug release from the produced magnetic nanoparticles can be modulated through the magnetic field time application.

Keywords: drug delivery, magnetic nanoparticles, PLGA nanoparticles, controlled release rate

Procedia PDF Downloads 242

Authors: T. Mohammed Chikouche, K. Hartani

Abstract:

Based on the analysis of basic direct torque control, a parallel master slave for four in-wheel permanent magnet synchronous motors (PMSM) fed by two three phase inverters used in electric vehicle is proposed in this paper. A conventional system with multi-inverter and multi-machine comprises a three phase inverter for each machine to be controlled. Another approach consists in using only one three-phase inverter to supply several permanent magnet synchronous machines. A modified direct torque control (DTC) algorithm is used for the control of the bi-machine traction system. Simulation results show that the proposed control strategy is well adapted for the synchronism of this system and provide good speed tracking performance.

Keywords: electric vehicle, multi-machine single-inverter system, multi-machine multi-inverter control, in-wheel motor, master-slave control

Procedia PDF Downloads 200

Authors: P. S. Jain, K. D. Bobade, S. J. Surana

Abstract:

A simple, selective, precise and Stability-indicating High-performance thin-layer chromatographic method for analysis of Naftopidil both in a bulk and in pharmaceutical formulation has been developed and validated. The method employed, HPTLC aluminium plates precoated with silica gel as the stationary phase. The solvent system consisted of hexane: ethyl acetate: glacial acetic acid (4:4:2 v/v). The system was found to give compact spot for Naftopidil (Rf value of 0.43±0.02). Densitometric analysis of Naftopidil was carried out in the absorbance mode at 253 nm. The linear regression analysis data for the calibration plots showed good linear relationship with r2=0.999±0.0001 with respect to peak area in the concentration range 200-1200 ng per spot. The method was validated for precision, recovery and robustness. The limits of detection and quantification were 20.35 and 61.68 ng per spot, respectively. Naftopidil was subjected to acid and alkali hydrolysis, oxidation and thermal degradation. The drug undergoes degradation under acidic, basic, oxidation and thermal conditions. This indicates that the drug is susceptible to acid, base, oxidation and thermal conditions. The degraded product was well resolved from the pure drug with significantly different Rf value. Statistical analysis proves that the method is repeatable, selective and accurate for the estimation of investigated drug. The proposed developed HPTLC method can be applied for identification and quantitative determination of Naftopidil in bulk drug and pharmaceutical formulation.

Keywords: naftopidil, HPTLC, validation, stability, degradation

Procedia PDF Downloads 380

Authors: Indu Verma, Santanu Kumar Pal

Abstract:

Interactions between DNA and adsorbed Poly (L-lysine) (PLL) on liquid crystal (LC) droplets were investigated using polarizing optical microcopy (POM) and epi-fluorescence microscopy. Earlier, we demonstrated that adsorption of PLL to the LC/aqueous interface resulted in homeotropic orientation of the LC and thus exhibited a radial configuration of the LC confined within the droplets. Subsequent adsorption of DNA (single stranded DNA/double stranded DNA) at PLL coated LC droplets was found to trigger a LC reorientation within the droplets leading to pre-radial/bipolar configuration of those droplets. To our surprise, subsequent exposure of complementary ssDNA (c-ssDNA) to ssDNA/ adsorbed PLL modified LC droplets did not cause the LC reorientation. This is likely due to the formation of polyplexes (DNA-PLL complex) as confirmed by fluorescence microscopy and atomic force microscopy. In addition, dsDNA adsorbed PLL droplets have been found to be effectively used to displace (controlled release) propidium iodide (a model drug) encapsulated within dsDNA over time. These observations suggest the potential for a label free droplet based LC detection system that can respond to DNA and may provide a simple method to develop DNA-based drug nano-carriers.

Keywords: DNA biosensor, drug delivery, interfaces, liquid crystal droplets

Procedia PDF Downloads 278

Authors: Aoxue Yang, Weili Tian, Yonghe Wu, Haikun Liu

Abstract:

Brain tumor stem cells (BTSCs) are resistant to therapy and give rise to recurrent tumors. These rare and elusive cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. The identification of dormant BTSCs is thus necessary to design effective therapies for glioblastoma (GBM) patients. Little progress has been made in therapeutic treatment of glioblastoma in the last decade despite rapid progress in molecular understanding of brain tumors1. Here we show that the stress hormone glucocorticoid is essential for the maintenance of brain tumor stem cells (BTSCs), which are resistant to conventional therapy. The glucocorticoid receptor (GR) regulates metabolic plasticity and chemoresistance of the dormant BTSC via controlling expression of GPD1 (glycerol-3-phosphate dehydrogenase 1), which is an essential regulator of lipid metabolism in BTSCs. Genomic, lipidomic and cellular analysis confirm that GR/GPD1 regulation is essential for BTSCs metabolic plasticity and survival. We further demonstrate that the GR agonist dexamethasone (DEXA), which is commonly used to control edema in glioblastoma, abolishes the effect of chemotherapy drug temozolomide (TMZ) by upregulating GPD1 and thus promoting tumor cell dormancy in vivo, this provides a mechanistic explanation and thus settle the long-standing debate of usage of steroid in brain tumor patient edema control. Pharmacological inhibition of GR/GPD1 pathway disrupts metabolic plasticity of BTSCs and prolong animal survival, which is superior to standard chemotherapy. Patient case study shows that GR antagonist mifepristone blocks tumor progression and leads to symptomatic improvement. This study identifies an important mechanism regulating cancer stem cell dormancy and provides a new opportunity for glioblastoma treatment.

Keywords: cancer stem cell, dormancy, glioblastoma, glycerol-3-phosphate dehydrogenase 1, glucocorticoid receptor, dexamethasone, RNA-sequencing, phosphoglycerides.

Procedia PDF Downloads 69

Authors: Samson F. Agberotimi, Rachel B. Asagba, Choja Oduaran

Abstract:

Disturbing rate of use of different substances such as cannabis, alcohol, as well as pharmaceutical drugs among Nigerian youth in recent times has been affirmed in the literature. There is, however, a paucity of literature addressing the pattern of usage of such drugs, especially for clinical relevance and intervention planning. The present study investigated the prevalence and pattern of drug usage among youth in Ogbomoso, Nigeria. A cross-sectional survey involving 92 purposively selected participants comprising of 82 males and 10 females aged between 15 and 24 years was conducted. A measure of drug involvement and demographic characteristics was administered to the participants. Descriptive analysis was done using the SPSS v.21. Cannabis (79.4%), alcohol (77.2%), codeine (70.7%), tobacco (65.2%) and tramadol (47.8%) are the five most frequently used substances. However, the majority of the users of tobacco (68.3%) and alcohol (62.0%) are casual users indicating a mild level of use of the substances among the participants. On the other hand, 49.2% of the codeine users, 27.3% of the tramadol users, and 21.9% of the cannabis users reported harmful/intensive levels of use. Furthermore, the results revealed individuals at the pathological level of use as 28.8% for cannabis, 25.0% for tramadol, and 21.6% for codeine, and thus require clinical/therapeutic intervention. In conclusion, cannabis remains the most frequently used substance among youths. However, there appears to be a shift from the use of conventional psychoactive substances to pharmaceutical/prescription drugs such as codeine and tramadol. The findings of this study raised the need for both preventive and therapeutic interventions addressing the problem of substance use disorder among youth in contemporary society.

Keywords: Ogbomoso, pattern of drug use, prevalence of drug use, youth

Procedia PDF Downloads 145

Authors: Sultan Noman Qasem

Abstract:

This paper presents an evolutionary algorithm for solving multi-objective optimization problems-based artificial neural network (ANN). The multi-objective evolutionary algorithm used in this study is genetic algorithm while ANN used is radial basis function network (RBFN). The proposed algorithm named memetic elitist Pareto non-dominated sorting genetic algorithm-based RBFNN (MEPGAN). The proposed algorithm is implemented on medical diseases problems. The experimental results indicate that the proposed algorithm is viable, and provides an effective means to design multi-objective RBFNs with good generalization capability and compact network structure. This study shows that MEPGAN generates RBFNs coming with an appropriate balance between accuracy and simplicity, comparing to the other algorithms found in literature.

Keywords: radial basis function network, hybrid learning, multi-objective optimization, genetic algorithm

Procedia PDF Downloads 540

Authors: Samashi Munaweera

Abstract:

Cancer stem cells (CSC) are responsible for the initiation, extensive proliferation and metastasis of cancer. CSCs, including breast cancer stem cells (bCSCs), have the capacity to generate chemo and radiotherapy resistance heterogeneous populations of cells. Over-expressed ABCB1 has been reported as a main reason for drug resistance of CSCs via activating drug efflux pumps by creating pores in the cell membrane. The overall efficiency of chemotherapeutic agents might be enhanced by blocking the ABCB protein efflux pump in the CSC membrane. There is an urgent need to search for persuasive natural drugs which can target CSCs. Anti-cancer properties of Hylocereus undatus on cancer CSCs have not yet been studied. In the present study, the anti-cancer effects of the peel and flesh of H. undatus fruit on bCSCs were evaluated with the aim of developing a marketable anti-cancer nutraceutical formulation. The flesh and peel of H. undatus were freeze-dried and sequentially extracted into four different solvents (hexane, chloroform, ethyl acetate and ethanol). All extracts (eight extracts) were dried under reduced pressure, and different concentrations (12.5-400 µg/mL) were treated on bCSCs isolated from a triple-negative chemo-resistant breast cancer phenotype (MDA-MB-231 cells). Anti-proliferative effects of all extracts and paclitaxel (positive control) were determined by a colorimetric assay (WST-1 based). Since peel-chloroform (IC50= 54.8 µg/mL) and flesh-ethyl acetate (IC50= 150.5 µg/mL) extras exerted a potent anti-proliferative effect at 72 h post-incubation, a combinatorial formulation (CF) was developed with the most active peel-chloroform extract and 20 µg/mL of verapamil (a known ABCB1 drug efflux pump blocker) first time in the world. Anti-proliferative effects and pro-apoptotic effects of CF were confirmed by estimating activated caspase3 and caspase7 levels and apoptotic morphological features in the CF-treated bCSCs compared to untreated and only verapamil (20 µg/mL) treated bCSCs, and CF-treated normal mammary epithelial cells (MCF-10A). The antiproliferative effects of CF (16.4 µg/mL) are greater than paclitaxel (19.2 µg/mL) and three folds greater than peel-chloroform extract (IC50= 54.8 µg/mL) on bCSCs while exerting fewer effects on normal cells (> 400 µg/mL). Collectively, CF can be considered as a potential initiative of a nutraceutical formulation that can target CSCs.

Keywords: cancer stem cells (CSC), breast cancer stem cells (bCSCs), anti-proliferative effects, verapamil, hylocereus undatus

Procedia PDF Downloads 4

Authors: Sweta Pandey, Samridhi Dhyani, Susmita Chaudhuri

Abstract:

Klebsiella pneumoniae causes a wide range of infections, including urinary tract infections, sepsis, bacteremia, pneumonia, and liver abscesses. The emergence of multi-drug resistance in this bacterium led to a major setback for clinical management. WHO also endorsed a need for finding alternative therapy to antibiotics for the treatment of these infections. Development of vaccines and passive antibody therapy has been proven as a potent alternative to antibiotics in the case of MDR, XDR, and PDR Klebsiella infections. Siderophore receptors have been demonstrated to be overexpressed for the internalization of iron siderophore complexes during infections in most Gram-negative bacteria. For the present study, immune response to siderophore receptors to establish this protein as a potential immunogen for the development of therapeutic leads was explored. Clinical strains of Klebsiella pneumoniae were grown in iron-deficient conditions, and the iron-regulated outer membrane proteins were extracted and characterized through mass spectrometry for specific identification. The gene for identified protein was cloned in pET- 28a vector and expressed in E. coli. The native protein and the recombinant protein were isolated and purified and used as antigens for the generation of immune response in BALB/c mice. The native protein of Klebsiella pneumoniae grown in iron-deficient conditions was identified as FepA (Ferrienterobactin receptor) and other siderophore receptors. This 80 kDa protein generated an immune response in BALB/c mice. The antiserum from mice after subsequent booster doses was collected and showed binding with FepA protein in western blot and phagocytic uptake of the K. pneumoniae in the presence antiserum from immunized mice also observed from the animal studies after bacterial challenge post immunisation in mice have shown bacterial clearance. The antiserum from mice showed binding and clearance of the Klebsiella pneumoniae bacteria in vitro and in vivo. These antigens used for generating an active immune response in mice can further be used for therapeutic monoclonal antibody development against Klebsiella pneumoniae infections.

Keywords: antiserum, FepA, Klebsiella pneumoniae, multi drug resistance, siderophore receptor

Procedia PDF Downloads 81

Authors: Nizar Jawad Hadi, Sajad Abd Alabbas

Abstract:

Because of their ability to encapsulate and release drugs in a controlled manner, microspheres fabricated from polymer emulsions using microfluidic devices have shown promise for drug delivery applications. In this study, the effects of velocity, density, viscosity, and surface tension, as well as channel diameter, on microsphere generation were investigated using Fluent Ansys software. The software was programmed with the physical properties of the polymer emulsion such as density, viscosity and surface tension. Simulation will then be performed to predict fluid flow and microsphere production and improve the design of drug delivery applications based on changes in these parameters. The effects of capillary and Weber numbers are also studied. The results of the study showed that the size of the microspheres can be controlled by adjusting the speed and diameter of the channel. Narrower microspheres resulted from narrower channel widths and higher flow rates, which could improve drug delivery efficiency, while smaller microspheres resulted from lower interfacial surface tension. The viscosity and density of the polymer emulsion significantly affected the size of the microspheres, ith higher viscosities and densities producing smaller microspheres. The loading and drug release properties of the microspheres created with the microfluidic technique were also predicted. The results showed that the microspheres can efficiently encapsulate drugs and release them in a controlled manner over a period of time. This is due to the high surface area to volume ratio of the microspheres, which allows for efficient drug diffusion. The ability to tune the manufacturing process using factors such as speed, density, viscosity, channel diameter, and surface tension offers a potential opportunity to design drug delivery systems with greater efficiency and fewer side effects.

Keywords: polymer emulsion, microspheres, numerical simulation, microfluidic device

Procedia PDF Downloads 45

Authors: Flavia Laffleur

Abstract:

Summary: Biomaterials have gained immense interest in the pharmaceutical research in the last decades. Hyaluronic acid a carbohydrate and mucopolysaccharide was chemically modified in order to achieve and establish a promising platform for buccal drug delivery. Aim: Novel biomaterial was tested for its potential for buccal drug delivery. Background: Polysaccharide hyaluronic acid (HA) was chemically modified with cysteine ethyl ether (CYS). By immobilization of the thiol-bearing ligand on the polymeric backbone the thiolated bioconjugate HA-CYS was obtained. Methodology: Mucoadhesive, permeation enhancing and stability potential as well as mechanical, physicochemical properties further mucoadhesive strength, swelling index and residence time were investigated. The developed thiolated bioconjugate displayed enhanced mucoadhesiveness on buccal mucosa as well as permeation behavior and polymer stability. The near neutral pH and negative cytotoxicity studies indicated their non-irritability and biocompatible nature with biological tissues. Further, the model drug sulforhodamine 101 was incorporated to determine its drug release profiles. Results: The synthesized thiomer showed no toxicity. The mucoadhesion of thiolated hyaluronic acid on buccal mucosa was significantly improved in comparison to unmodified one. The biomaterial showed 2.5-fold higher stability in polymer structure. The release of sulforhodamine in the presence of thiolated hyaluronic acid was 2.3-fold increased compared to hyaluronic acid. Conclusion: Thus, the promising results encourage further investigations and exploitation of this versatile polysaccharide. So far, hyaluronic acid was not evaluated for buccal drug delivery.

Keywords: buccal delivery, hyaluronic acid, mucoadhesion, thiomers

Procedia PDF Downloads 485

Authors: Polina Prokopovich

Abstract:

Disease-modifying osteoarthritis drugs (DMOADs) are a new therapeutic class for OA, preventing or inhibiting OA development. Unfortunately, none of the DMOADs have been clinically approved due to their poor therapeutic effects in clinical trials. The joint environment has played a role in the poor clinical performance of these drugs by limiting the amount of drug effectively delivered as well as the time that the drug spends within the joint space. The current study aims to enhance the cartilage uptake and retention time of the DMOADs-model (licofelone), which showed a significant therapeutic effect against OA progression and is currently in phase III. Licofelone will be covalently conjugated to the hydrolysable, cytocompatible, and cationic poly beta-amino ester polymers (PBAE). The cationic polymers (A16 and A87) can be electrostatically attached to the negatively charged cartilage component (glycosaminoglycan), which will increase the drug penetration through the cartilage and extend the drug time within the cartilage. In the cartilage uptake and retention time studies, an increase of 18 to 37 times of the total conjugated licofelone to A87 and A16 was observed when compared to the free licofelone. Furthermore, the conjugated licofelone to A87 was detectable within the cartilage at 120 minutes, while the free licofelone was not detectable after 60 minutes. Additionally, the A87-licofelone conjugate showed no effect on the chondrocyte viability. In conclusion, the cationic A87 and A16 polymers increased the percentage of licofelone within the cartilage, which could potentially enhance the therapeutic effect and pharmacokinetic performance of licofelone or other DMOADs clinically.

Keywords: PBAE, cartilage., osteoarthritis, injectable biomaterials, drug delivery

Procedia PDF Downloads 53

Authors: Yuvraj Singh Dangi, Brajesh Kumar Tiwari, Ashok Kumar Jain, Kamta Prasad Namdeo

Abstract:

The potential use of liposomes as drug carriers by i.v. injection is limited by their low stability in blood stream. Firstly, phospholipid exchange and transfer to lipoproteins, mainly HDL destabilizes and disintegrates liposomes with subsequent loss of content. To avoid the pain associated with injection and to obtain better patient compliance studies concerning various dosage forms, have been developed. Conventional liposomes (unilamellar and multilamellar) have certain drawbacks like low entrapment efficiency, stability and release of drug after single breach in external membrane, have led to the new type of liposomal systems. The challenge has been successfully met in the form of Double Liposomes (DL). DL is a recently developed type of liposome, consisting of smaller liposomes enveloped in lipid bilayers. The outer lipid layer of DL can protect inner liposomes against various enzymes, therefore DL was thought to be more effective than ordinary liposomes. This concept was also supported by in vitro release characteristics i.e. DL formation inhibited the release of drugs encapsulated in inner liposomes. DL consists of several small liposomes encapsulated in large liposomes, i.e., multivesicular vesicles (MVV), therefore, DL should be discriminated from ordinary classification of multilamellar vesicles (MLV), large unilamellar vesicles (LUV), small unilamellar vesicles (SUV). However, for these liposomes, the volume of inner phase is small and loading volume of water-soluble drugs is low. In the present study, the potential of phosphatidylethanolamine (PE) lipid anchored double liposomes (DL) to incorporate two drugs in a single system is exploited as a tool to augment the H. pylori eradication rate. Preparation of DL involves two steps, first formation of primary (inner) liposomes by thin film hydration method containing one drug, then addition of suspension of inner liposomes on thin film of lipid containing the other drug. The success of formation of DL was characterized by optical and transmission electron microscopy. Quantitation of DL-bacterial interaction was evaluated in terms of percent growth inhibition (%GI) on reference strain of H. pylori ATCC 26695. To confirm specific binding efficacy of DL to H. pylori PE surface receptor we performed an agglutination assay. Agglutination in DL treated H. pylori suspension suggested selectivity of DL towards the PE surface receptor of H. pylori. Monotherapy is generally not recommended for treatment of a H. pylori infection due to the danger of development of resistance and unacceptably low eradication rates. Therefore, combination therapy with amoxicillin trihydrate (AMOX) as anti-H. pylori agent and ranitidine bismuth citrate (RBC) as antisecretory agent were selected for the study with an expectation that this dual-drug delivery approach will exert acceptable anti-H. pylori activity.

Keywords: Helicobacter pylorI, amoxicillin trihydrate, Ranitidine Bismuth citrate, phosphatidylethanolamine, multi vesicular systems

Procedia PDF Downloads 183

Authors: Salvana P. M. Costa, Tarcyla A. Gomes, Giovanna C. R. M. Schver, Leslie R. M. Ferraz, Cristovão R. Silva, Magaly A. M. Lyra, Danilo A. F. Fonte, Larissa A. Rolim, Amanda C. Q. M. Vieira, Miracy M. Albuquerque, Pedro J. Rolim-neto

Abstract:

Efavirenz (EFV) is considered one of the most widely used anti-HIV drugs. However, it is classified as a drug class II (poorly soluble, highly permeable) according to the biopharmaceutical classification system, presenting problems of absorption in the gastrointestinal tract and thereby inadequate bioavailability for its therapeutic action. This study aimed to overcome these barriers by developing and obtaining solid dispersions (SD) in order to increase the EFZ bioavailability. For the development of SD with EFV, theoretical and practical studies were initially performed. Thus, there was a choice of a carrier to be used. For this, it was analyzed the various criteria such as glass transition temperature of the polymer, intra- and intermolecular interactions of hydrogen bonds between drug and polymer, the miscibility between the polymer and EFV. The choice of the obtainment method of the SD came from the analysis of which method is the most consolidated in both industry and literature. Subsequently, the choice of drug and carrier concentrations in the dispersions was carried out. In order to obtain DS to present the drug in its amorphous form, as the DS were obtained, they were analyzed by X-ray diffraction (XRD). SD are more stable the higher the amount of polymer present in the formulation. With this assumption, a SD containing 10% of drug was initially prepared and then this proportion was increased until the XRD showed the presence of EFV in its crystalline form. From this point, it was not produced SD with a higher concentration of drug. Thus, it was allowed to select PVP-K30, PVPVA 64 and the SOLUPLUS formulation as carriers, once it was possible the formation of hydrogen bond between EFV and polymers since these have hydrogen acceptor groups capable of interacting with the donor group of the drug hydrogen. It is worth mentioning also that the films obtained, independent of concentration used, were presented homogeneous and transparent. Thus, it can be said that the EFV is miscible in the three polymers used in the study. The SD and Physical Mixtures (PM) with these polymers were prepared by the solvent method. The EFV diffraction profile showed main peaks at around 2θ of 6,24°, in addition to other minor peaks at 14,34°, 17,08°, 20,3°, 21,36° and 25,06°, evidencing its crystalline character. Furthermore, the polymers showed amorphous nature, as evidenced by the absence of peaks in their XRD patterns. The XRD patterns showed the PM overlapping profile of the drug with the polymer, indicating the presence of EFV in its crystalline form. Regardless the proportion of drug used in SD, all the samples showed the same characteristics with no diffraction peaks EFV, demonstrating the behavior amorphous products. Thus, the polymers enabled, effectively, the formation of amorphous SD, probably due to the potential hydrogen bonds between them and the drug. Moreover, the XRD analysis showed that the polymers were able to maintain its amorphous form in a concentration of up to 80% drug.

Keywords: amorphous form, Efavirenz, solid dispersions, solubility

Procedia PDF Downloads 547

Authors: Babek Erdebilli

Abstract:

The aim of this study is to develop and describe a new methodology for the Multi-Criteria Decision-Making (MCDM) problem using IFE (Elimination Et Choix Traduisant La Realite (ELECTRE) model. The proposed models enable Decision-Makers (DMs) on the assessment and use Intuitionistic Fuzzy Numbers (IFN). A numerical example is provided to demonstrate and clarify the proposed analysis procedure. Also, an empirical experiment is conducted to validation the effectiveness.

Keywords: multi-criteria decision-making, IFE, DM’s, fuzzy electre model

Procedia PDF Downloads 624

Authors: Sanghoon Park, Ki-Jin Kim, Kwang-Ho Ahn

Abstract:

This paper discusses the undesirable charge transfer through the parasitic capacitances of the input transistors in a multi-inputs voltage sense amplifier. Its intrinsic rail-to-rail voltage transitions at the output nodes inevitably disturb the input sides through the capacitive coupling between the outputs and inputs. Then, it can possible degrade the stabilities of the reference voltage levels. Moreover, it becomes more serious in multi-channel systems by altering them for other channels, and so degrades the linearity of the overall systems. In order to alleviate the internal node voltage transition, the internal node stabilization techniques are proposed. It achieves 45% and 40% improvements for node stabilization and input referred disturbance, respectively.

Keywords: voltage sense amplifier, multi-inputs, voltage transition, node stabilization, biasing circuits

Procedia PDF Downloads 544

Authors: M. R. Aher, R. B. Laware, G. S. Asane, B. S. Kuchekar

Abstract:

Objective: Studies have shown that a new combination therapy with Artemisinin derivatives and curcumin is unique, with potential advantages over known ACTs. In present study an attempt was made to prepare microparticulate drug delivery system of Curcumin-Zn complex and evaluate it in combination with artemether for antimalarial activity. Material and method: Curcumin Zn complex was prepared and encapsulated using sodium alginate. Microparticles thus obtained are further coated with various enteric polymers at different coating thickness to control the release. Microparticles are evaluated for encapsulation efficiency, drug loading and in vitro drug release. Roentgenographic Studies was conducted in rabbits with BaSO 4 tagged formulation. Optimized formulation was screened for antimalarial activity using P. berghei-infected mice survival test and % paracetemia inhibition, alone (three oral dose of 5mg/day) and in combination with arthemether (i.p. 500, 1000 and 1500µg). Curcumin-Zn(II) was estimated in serum after oral administration to rats by using spectroflurometry. Result: Microparticles coated with Cellulose acetate phthalate showed most satisfactory and controlled release with 479 min time for 60% drug release. X-ray images taken at different time intervals confirmed the retention of formulation in GI tract. Estimation of curcumin in serum by spectroflurometry showed that drug concentration is maintained in the blood for longer time with tmax of 6 hours. The survival time (40 days post treatment) of mice infected with P. berghei was compared to survival after treatment with either Curcumin-Zn(II) microparticles artemether combination, curcumin-Zn complex and artemether. Oral administration of Curcumin-Zn(II)-artemether prolonged the survival of P.berghei-infected mice. All the mice treated with Curcumin-Zn(II) microparticles (5mg/day) artemether (1000µg) survived for more than 40 days and recovered with no detectable parasitemia. Administration of Curcumin-Zn(II) artemether combination reduced the parasitemia in mice by more than 90% compared to that in control mice for the first 3 days after treatment. Conclusion: Antimalarial activity of the curcumin Zn-artemether combination was more pronounced than mono therapy. A single dose of 1000µg of artemether in curcumin-Zn combination gives complete protection in P. berghei-infected mice. This may reduce the chances of drug resistance in malaria management.

Keywords: formulation, microparticulate drug delivery, antimalarial, pharmaceutics

Procedia PDF Downloads 376

Authors: Salma E. Ahmed

Abstract:

Since the mid 50’s, enormous attention has been paid towards nanocarriers and their applications in drug and gene delivery. Among these vesicles, liposomes and micelles have been heavily investigated due to their many advantages over other types. Liposomes, for instance, are mostly distinguished by their ability to encapsulate hydrophobic, hydrophilic and amphiphilic drugs. Micelles, on the other hand, are self-assembled shells of lipids, amphiphilic or oppositely charged block copolymers that, once exposed to aqueous media, can entrap hydrophobic agents, and possess prolonged circulation in the bloodstream. Both carriers are considered compatible and biodegradable. Nevertheless, they have limited stabilities, chemical versatilities, and drug encapsulation efficiencies. In order to overcome these downsides, strategies for optimizing a novel drug delivery system that has the architecture of liposomes and polymeric characteristics of micelles have been evolved. Polymersomes are vehicles with fluidic cores and hydrophobic shells that are protected and isolated from the aqueous media by the hydrated hydrophilic brushes which give the carrier its distinctive polymeric bilayer shape. Similar to liposomes, this merit enables the carrier to encapsulate a wide range of agents, despite their affinities and solubilities in water. Adding to this, the high molecular weight of the amphiphiles that build the body of the polymersomes increases their colloidal and chemical stabilities and reduces the permeability of the polymeric membranes, which makes the vesicles more protective to the encapsulated drug. These carriers can also be modified in ways that make them responsive when targeted or triggered, by manipulating their composition and attaching moieties and conjugates to the body of the carriers. These appealing characteristics, in addition to the ease of synthesis, gave the polymersomes greater potentials in the area of drug delivery. Thus, their design and characterization, in comparison with liposomes and micelles, are briefly reviewed in this work.

Keywords: controlled release, liposomes, micelles, polymersomes, targeting

Procedia PDF Downloads 177

Authors: Ammar Asma, Bouafia Nabiha, Ghammam Rim, Ezzi Olfa, Ben Cheikh Asma, Mahjoub Mohamed, Helali Radhia, Sma Nesrine, Chouchène Imed, Boussarsar Hamadi, Njah Mansour

Abstract:

Background: Central venous catheter associated infections (CVC-AI) are among the serious hospital-acquired infections. The aims of this study are to determine the incidence of CVC-AI, and their risk factors among patients followed in a Tunisian medical intensive care unit (ICU). Materials / Methods: A prospective cohort study conducted between September 15th, 2015 and November 15th, 2016 in an 8-bed medical ICU including all patients admitted for more than 48h. CVC-AI were defined according to CDC of ATLANTA criteria. The enrollment was based on clinical and laboratory diagnosis of CVC-AI. For all subjects, age, sex, underlying diseases, SAPS II score, ICU length of stay, exposure to CVC (number of CVC placed, site of insertion and duration catheterization) were recorded. Risk factors were analyzed by conditional stepwise logistic regression. The p-value of < 0.05 was considered significant. Results: Among 192 eligible patients, 144 patients (75%) had a central venous catheter. Twenty-eight patients (19.4%) had developed CVC-AI with density rate incidence 20.02/1000 CVC-days. Among these infections, 60.7% (n=17) were systemic CVC-AI (with negative blood culture), and 35.7% (n=10) were bloodstream CVC-AI. The mean SAPS II of patients with CVC-AI was 32.76 14.48; their mean Charlson index was 1.77 1.55, their mean duration of catheterization was 15.46 10.81 days and the mean duration of one central line was 5.8+/-3.72 days. Gram-negative bacteria was determined in 53.5 % of CVC-AI (n= 15) dominated by multi-drug resistant Acinetobacter baumani (n=7). Staphylococci were isolated in 3 CVC-AI. Fourteen (50%) patients with CVC-AI died. Univariate analysis identified men (p=0.034), the referral from another hospital department (p=0.03), tobacco (p=0.006), duration of sedation (p=0.003) and the duration of catheterization (p=0), as possible risk factors of CVC-AI. Multivariate analysis showed that independent factors of CVC-AI were, male sex; OR= 5.73, IC 95% [2; 16.46], p=0.001, Ramsay score; OR= 1.57, IC 95% [1.036; 2.38], p=0.033, and duration of catheterization; OR=1.093, IC 95% [1.035; 1.15], p=0.001. Conclusion: In a monocenter cohort, CVC-AI had a high density and is associated with poor outcome. Identifying the risk factors is necessary to find solutions for this major health problem.

Keywords: central venous catheter associated infection, intensive care unit, prospective cohort studies, risk factors

Procedia PDF Downloads 344

Authors: Kalaumari Mayoral-Peña, Ana I. Montejano-Montelongo, Josué Reyes-Muñoz, Gonzalo A. Ortiz-Mancilla, Mayrin Rodríguez-Cruz, Víctor Hernández-Villalobos, Jesús A. Guzmán-López, Santiago García-Jacobo, Iván Licona-Vázquez, Grisel Fierros-Romero, Rosario Flores-Vallejo

Abstract:

The group B-lactamic antibiotics include some of the most frequently used small drug molecules against bacterial infections. Nevertheless, an alarming decrease in their efficacy has been reported due to the emergence of antibiotic-resistant bacteria. Infections caused by bacteria expressing extended Spectrum B-lactamases (ESBLs) are difficult to treat and account for higher morbidity and mortality rates, delayed recovery, and high economic burden. According to the Global Report on Antimicrobial Resistance Surveillance, it is estimated that mortality due to resistant bacteria will ascend to 10 million cases per year worldwide. These facts highlight the importance of developing low-cost and readily accessible detection methods of drug-resistant ESBLs bacteria to prevent their spread and promote accurate and fast diagnosis. Bacterial detection is commonly done using molecular diagnostic techniques, where PCR stands out for its high performance. However, this technique requires specialized equipment not available everywhere, is time-consuming, and has a high cost. Loop-Mediated Isothermal Amplification (LAMP) is an alternative technique that works at a constant temperature, significantly decreasing the equipment cost. It yields double-stranded DNA of several lengths with repetitions of the target DNA sequence as a product. Although positive and negative results from LAMP can be discriminated by colorimetry, fluorescence, and turbidity, there is still a large room for improvement in the point-of-care implementation. DNA origami is a technique that allows the formation of 3D nanometric structures by folding a large single-stranded DNA (scaffold) into a determined shape with the help of short DNA sequences (staples), which hybridize with the scaffold. This research aimed to generate DNA origami structures using LAMP products as scaffolds to improve the sensitivity to detect ESBLs in point-of-care diagnosis. For this study, the coding sequence of the CTM-X-15 ESBL of E. coli was used to generate the LAMP products. The set of LAMP primers were designed using PrimerExplorerV5. As a result, a target sequence of 200 nucleotides from CTM-X-15 ESBL was obtained. Afterward, eight different DNA origami structures were designed using the target sequence in the SDCadnano and analyzed with CanDo to evaluate the stability of the 3D structures. The designs were constructed minimizing the total number of staples to reduce costs and complexity for point-of-care applications. After analyzing the DNA origami designs, two structures were selected. The first one was a zig-zag flat structure, while the second one was a wall-like shape. Given the sequence repetitions in the scaffold sequence, both were able to be assembled with only 6 different staples each one, ranging between 18 to 80 nucleotides. Simulations of both structures were performed using scaffolds of different sizes yielding stable structures in all the cases. The generation of the LAMP products were tested by colorimetry and electrophoresis. The formation of the DNA structures was analyzed using electrophoresis and colorimetry. The modeling of novel detection methods through bioinformatics tools allows reliable control and prediction of results. To our knowledge, this is the first study that uses LAMP products and DNA-origami in combination to delect ESBL-producing bacterial strains, which represent a promising methodology for diagnosis in the point-of-care.

Keywords: beta-lactamases, antibiotic resistance, DNA origami, isothermal amplification, LAMP technique, molecular diagnosis

Procedia PDF Downloads 193

Authors: Burcu Doymus, Fatma N. Kok, Sakip Onder

Abstract:

Titanium and titanium-based materials are commonly used to replace or regenerate the injured or lost tissues because of accidents or illnesses. Hospital infections and strong bond formation at the implant-tissue interface are directly affecting the success of the implantation as weak bonding with the native tissue and hospital infections lead to revision surgery. The purpose of the presented study is to modify the surface of the titanium substrates with nano/microspheres for local drug delivery and to prevent hospital infections. Firstly, titanium surfaces were silanized with APTES (3-Triethoxysilylpropylamine) following the negatively charged oxide layer formation. Then characterization studies using Scanning Electron Microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) were done on the modified surfaces. Secondly, microspheres/nanospheres were prepared with chitosan that is a natural polymer and having valuable properties such as non-toxicity, high biocompatibility, low allergen city and biodegradability for biomedical applications. Antibiotic (ciprofloxacin) loaded micro/nanospheres have been fabricated using emulsion cross-linking method and have been immobilized onto the titanium surfaces with different immobilization techniques such as covalent bond and entrapment. Optimization studies on size and drug loading capacities of micro/nanospheres were conducted before the immobilization process. Light microscopy and SEM were used to visualize and measure the size of the produced micro/nanospheres. Loaded and released drug amounts were determined by using UV- spectrophotometer at 278 nm. Finally, SEM analysis and drug release studies on the micro/nanospheres coated Ti surfaces were done. As a conclusion, it was shown that micro/nanospheres were immobilized onto the surfaces successfully and drug release from these surfaces was in a controlled manner. Moreover, the density of the micro/nanospheres after the drug release studies was higher on the surfaces where the entrapment technique was used for immobilization. Acknowledgement: This work is financially supported by The Scientific and Technological Research Council Of Turkey (Project # 217M220)

Keywords: chitosan, controlled drug release, nanosphere, nosocomial infections, titanium

Procedia PDF Downloads 110

Authors: Shahul Hamid Khan, S. Santhosh, Abhinav Kumar Sharma

Abstract:

Environmental performance along with social performance is becoming vital factors for industries to achieve global standards. With a good environmental policy global industries are differentiating them from their competitors. This paper concentrates on multi stage, multi product and multi period manufacturing network. Bi-objective mathematical models for total cost and total emission for the entire forward supply chain are considered. Here five different problems are considered by varying the number of suppliers, manufacturers, and environmental levels, for illustrating the taken mathematical model. GA, and Random search are used for finding the optimal solution. The input parameters of the optimal solution are used to find the tradeoff between the initial investment by the industry and the long term benefit of the environment.

Keywords: closed loop supply chain, genetic algorithm, random search, green supply chain

Procedia PDF Downloads 527

Authors: Behcet Al, Şener Cindoruk, Suat Zengin, Mehmet Murat Oktay, Mehmet Mustafa Sunar, Hatice Eroglu, Cuma Yildirim

Abstract:

Objective: In present study we aimed to investigate the chronic drug use due to chronic diseases in patients admitted to emergency department. Materials-Methods: 144 patients who applied to emergency department (ED) of medicine school of Gaziantep University between June 2013 and September 2013 with chronic diseases and use chronic drugs were included. Information about drugs used by patients were recorded. Results: Of patients, half were male, half were female, and the mean age was 58 years. The first three common diseases were diabetes mellitus, hypertension and coronary artery diseases. Of patients, %79.2 knew their illness. Fifty patients began to use drug within three months, 36 patient began to use within the last one year. While 42 patients brought all of their drugs with themselves, 17 patients brought along a portion of drugs. While three patients stopped their medication completely, 125 patients received medication on a regular basis. Fifty-two patient described the drugs with names, 13 patients described with their colors, 3 patients described by grammes, 45 patients described with the size of the tablet and 13 patients could not describe the drugs. Ninety-two patients explained which kind of drugs were used for each diseases, 17 patient explained partly, and 35 patients had no idea. Hundred patients received medication by themselves, 44 patients medications were giving by their relatives and med carers. Of medications, 140 were written by doctors directly, three medication were given by pharmacist; and one patient bought the drug by himself. For 11 patients the drugs were not harmonious to their diseases. Fifty-one patients admitted to the ED two times within last week, and 73 admitted two times within last month. Conclusion: The majority of patients with chronic diseases and use chronic drugs know their diseases and use the drugs in order, but do not have enough information about their medication.

Keywords: chronic disease, drug use, emergency department, medication

Procedia PDF Downloads 442